Clinical significance of circulating tumor cells in predicating the outcomes of patients with colorectal cancer

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The activities of SOD, CAT, GSH-Px and NOS in placentas from NC group, SP-A group, SP-A+ov-STOX1 group and SP-A+si-STOX1 group were shown (n = 6)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Xiafang Li, Chunnian Zhang" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Xiafang" "apellidos" => "Li" ] 1 => array:2 [ "nombre" => "Chunnian" "apellidos" => "Zhang" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "HIGHLIGHTS" "clase" => "author-highlights" "resumen" => "<ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001">•SP-A induced pathological damage to placenta by promoting STOX1.</li><li class="elsevierStyleListItem" id="celistitem0002">•SP-A inhibited the activities of antioxidant enzymes through STOX1.</li><li class="elsevierStyleListItem" id="celistitem0003">•SP-A promoted the ROS production in placenta by promoting STOX1.</li><li class="elsevierStyleListItem" id="celistitem0004">•SP-A inhibited protein levels of NOS3 and ARG2 in placenta.</li></ul>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S180759322203280X?idApp=UINPBA00004N" "url" => "/18075932/000000770000000C/v3_202308251443/S180759322203280X/v3_202308251443/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S1807593222032823" "issn" => "18075932" "doi" => "10.1016/j.clinsp.2022.100081" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "100081" "copyright" => "HCFMUSP" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Clinics. 2022;77C:" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original articles" "titulo" => "Long non-coding RNA SNHG1 promotes bladder cancer progression by upregulating EZH2 and repressing KLF2 transcription" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "en" ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0001" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2973 "Ancho" => 2333 "Tamanyo" => 373868 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "SNHG1 was highly expressed in BC. A, The expression of SNHG1 in BLCA data from TCGA (left) and fresh frozen specimen (right). B, SNHG1 expression in GSE7476 and GSE65635. C, SNHG1 expression in BLCA from TCGA database were shown in disparate histological subtypes or different stages. D, The prognostic value of SNHG1 was predicted by Kaplan-Meier analysis. E, The ROC curve analysis of SNHG1. F, SNHG1 expression in BC tissues and adjacent tissues. G, SNHG1 expression in BC cells and SV-HUC1 cells. H, The subcellular localization of SNHG1 in 5637 cells and J827 cells. Statistical significance was assessed using t test for two groups or one-way ANOVA for multiple groups. *p < 0.05; **p < 0.01; ***p < 0.001." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jie Min, Jiaxing Ma, Qi Wang, Dexin Yu" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Jie" "apellidos" => "Min" ] 1 => array:2 [ "nombre" => "Jiaxing" "apellidos" => "Ma" ] 2 => array:2 [ "nombre" => "Qi" "apellidos" => "Wang" ] 3 => array:2 [ "nombre" => "Dexin" "apellidos" => "Yu" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Highlights" "clase" => "author-highlights" "resumen" => "<ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001">•lncRNA SNHG1 played an oncogenic role in bladder cancer, indicating poor prognosis.</li><li class="elsevierStyleListItem" id="celistitem0002">•SNHG1 competitively bound miR-137-3p to promote EZH2 expression in the cytoplasm.</li><li class="elsevierStyleListItem" id="celistitem0003">•SNHG1 could interact with EZH2 to inhibit KLF2 transcription in the nucleus.</li></ul>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222032823?idApp=UINPBA00004N" "url" => "/18075932/000000770000000C/v3_202308251443/S1807593222032823/v3_202308251443/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original articles" "titulo" => "Clinical significance of circulating tumor cells in predicating the outcomes of patients with colorectal cancer" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Kehe Chen, Zhenxiang Chen, Mei Ou, Junping Wang, Xiao Huang, Yingying Wu, Wenhe Zhong, Jiao Yang, Jinging Huang, Min Huang, Deng Pan" "autores" => array:11 [ 0 => array:3 [ "nombre" => "Kehe" "apellidos" => "Chen" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "1" "identificador" => "fn1" ] ] ] 1 => array:3 [ "nombre" => "Zhenxiang" "apellidos" => "Chen" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "1" "identificador" => "fn1" ] ] ] 2 => array:2 [ "nombre" => "Mei" "apellidos" => "Ou" ] 3 => array:2 [ "nombre" => "Junping" "apellidos" => "Wang" ] 4 => array:2 [ "nombre" => "Xiao" "apellidos" => "Huang" ] 5 => array:2 [ "nombre" => "Yingying" "apellidos" => "Wu" ] 6 => array:2 [ "nombre" => "Wenhe" "apellidos" => "Zhong" ] 7 => array:2 [ "nombre" => "Jiao" "apellidos" => "Yang" ] 8 => array:2 [ "nombre" => "Jinging" "apellidos" => "Huang" ] 9 => array:2 [ "nombre" => "Min" "apellidos" => "Huang" ] 10 => array:4 [ "nombre" => "Deng" "apellidos" => "Pan" "email" => array:1 [ 0 => "pandeng@163.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0001" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Medical Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China" "identificador" => "aff0001" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0001" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0002" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1830 "Ancho" => 1708 "Tamanyo" => 120596 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0002" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Comparsion of CTCs and subtypes in CRC patients and control patients. (A) Total CTC number comparison; (B) Epithelial CTC number comparison; (C) Mixed CTC number comparison; (D) MCTC number comparison. CTCs, Circulating Tumor Cells; MCTC, Mesenchyal Circulating Tumor Cell." ] ] ] "textoCompleto" => "IntroductionWorldwide, Colorectal Cancer (CRC) is the fourth most lethal cancer after lung, stomach, and liver cancer.<a class="elsevierStyleCrossRef" href="#bib0001">1</a> Its incidence ranks second cancer in women and third cancer in men.<a class="elsevierStyleCrossRef" href="#bib0002">2</a> Bad eating habits, smoking, insufficient physical exercise, and obesity are the most common risk factors for the occurrence of CRC.<a class="elsevierStyleCrossRef" href="#bib0003">3</a> In addition, the patients with hereditary nonpolyposis colorectal cancer (HNPCC<a class="elsevierStyleCrossRef" href="#bib0004">4</a> or Lynch syndrome) and inflammatory bowel disease<a class="elsevierStyleCrossRef" href="#bib0005">5</a> also have a risk for this disease. CRC treatments include surgery, chemotherapy, radiotherapy, and immunotherapy, which are very useful for those patients with mismatch repair deficiency and microsatellite instability.<a class="elsevierStyleCrossRef" href="#bib0006">6</a>,<a class="elsevierStyleCrossRef" href="#bib0007">7</a>Although diagnosis and treatments of CRC had great progress in the past decades, its long-term survival rate is less than 60% or more low.<a class="elsevierStyleCrossRef" href="#bib0004">4</a> The survival rate of CRC is directly related to the types and Tumor-Node-Metastasis (TNM stages) of CRC.<a class="elsevierStyleCrossRef" href="#bib0008">8</a> In addition, the survival rate of CRC is also linked to specific gene expressions such as HSPA1A and RBM3.<a class="elsevierStyleCrossRef" href="#bib0009">9</a> Recent studies revealed that the presence of Circulation Tumor Cells (CTCs) in cancer patients was closely associated with the relapse and metastasis of cancer.<a class="elsevierStyleCrossRefs" href="#bib0010">10–12</a> CTCs are cells originally from a primary tumor and can become seeds for tumor growth in distant organs by blood circulation system.<a class="elsevierStyleCrossRef" href="#bib0013">13</a>,<a class="elsevierStyleCrossRef" href="#bib0014">14</a> This mechanism was the reason for the recurrence and metastasis of many cancers such as breast cancer,<a class="elsevierStyleCrossRef" href="#bib0015">15</a> lung cancer,<a class="elsevierStyleCrossRef" href="#bib0016">16</a> gastric cancer,<a class="elsevierStyleCrossRef" href="#bib0017">17</a> head and neck cancers,<a class="elsevierStyleCrossRefs" href="#bib0018">18–20</a> as well as resistance to anti-cancer treatment.In contrast, CTC-based liquid biopsies have a few advantages over traditional method.<a class="elsevierStyleCrossRef" href="#bib0021">21</a>,<a class="elsevierStyleCrossRef" href="#bib0022">22</a> First, it is a non-invasive and repeatable technique for monitoring metastasis, progress, and therapeutic efficiency of cancer.<a class="elsevierStyleCrossRef" href="#bib0023">23</a> Second, cell resources are from the peripheral blood of the patients and are easily obtained in the solid tumor.<a class="elsevierStyleCrossRef" href="#bib0024">24</a> Third, the CTC detections of solid tumors avoid surgery for evaluating metastasis of cancer.<a class="elsevierStyleCrossRef" href="#bib0025">25</a> Therefore, monitoring changes of CTCs in cancer patients have a great clinical value in assessing diagnosis, therapy, relapse, metastasis, and prognosis of cancer patients. In our study, the authors aim to investigate the correlation between CTCs profiles and the clinical features of CRC.Materials and methodsSubjects and samplesA total of 48 CRC and 20 patients without tumors as a control were enrolled in this study from January 2018 to October 2020. The diagnosis of these patients was confirmed by pathological and radiological findings from surgery or biopsy samples. TNM staging system for CRC patients followed the criteria of the American Joint Committee on Cancer (AJCC) 8th edition.<a class="elsevierStyleCrossRef" href="#bib0002">2</a> Those patients outside of the studied hospital or without tumor tissue available were excluded from this study. All participants also must meet the following criteria: no active infection and normal liver, kidney, and cardiology functions. A total of 5 milliliters (mL) of whole blood samples from patients were collected before or after treatments. All clinical characteristics of patients were documented and identified. All patients also followed up for their PFS and Overall Survival (OS). PFS was calculated as the time from the initial treatment to disease progression. OS is the time from the initial treatment to death. Tumor burden were counted using clinical and imaging data like Computer Tomography (CT) or Magnetic Resonance Imaging (MRI).The study protocol was reviewed and approved by the ethics committee of the people's hospital of Guangxi Zhuang autonomous region. Written informed consent has obtained from all patients before the study. All procedures performed in the studies were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments or comparable ethical standards.Isolation and identification of CTCsA filtration method was applied to isolate and identify CTCs following the previous technique.<a class="elsevierStyleCrossRef" href="#bib0026">26</a>,<a class="elsevierStyleCrossRef" href="#bib0027">27</a> Briefly, blood samples were collected before and after treatment. Red blood cells were removed using a red blood cell lysis buffer (154 mM NH4Cl, 10 mM KHCO3, and 0.1 mM EDTA) and incubated for 30 minutes at room temperature. The remaining cells were fixed containing 4% formaldehyde (Sigma, St. Louis, USA) with Phosphate Buffered Saline (PBS) solution for 5 minutes. Then the cells were transferred to the filtration tube with an 8 μM pore size filter membrane for the manifold vacuum plate and started to filtrate CTCs.Tri-color RNA in situ hybridization assayThe RNA-in situ hybridization<a class="elsevierStyleCrossRef" href="#bib0025">25</a> technique based on the branched DNA (bDNA) signal amplification system<a class="elsevierStyleCrossRef" href="#bib0028">28</a> was applied to characterize CTCs. Briefly, bDNA capture probe is used to bind > 30 specific nucleotide sequences called Label Extenders (LEs) of an interested gene, which LE probes bind preamplifiers. In turn, preamplifiers bind many amplifiers and the label probe, which are the Alexa Fluor 594 conjugated epithelial biomarkers EpCAM and CK8/18/19, Alexa Fluor 488 conjugated mesenchymal biomarkers vimentin and twist, and 4′,6-Diamidino-2-Phenylindole 9 (DAPI) staining. The results are that low up to 10 copies of original specific gene sequences can be accurately amplified between ∼10,000 and 10,000,000 fold. In addition, these fluorescents labeled antibodies are easily observed and counted in a fluorescent microscope.Statistical analysisData were analyzed using statistic analyzing Excel and GraphPad Prism8 software. The χ2 test, t-test, and Kaplan-Meier analysis were performed to analyze the data; p < 0.05 was considered a significant difference.ResultsPatients and CTC characteristicsA total of 48 CRC patients and 20 free-tumor control patients were recruited for this study. The detailed patient characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>. Their average age was 52.42 years old and the range was from 20‒80 years old, including 26 males and 22 females. The number of patients from the cecum, ascending colon, transverse colon, descending colon, and sigmoid colon were 3, 7, 5, 5, and 28, respectively. Stage II, III, and IV patient numbers were 28, 12, and 8, respectively. Low, moderate, and well differentiation patients were 6, 35, and 7, respectively. Twenty patients had metastatic disease, including 13 cases of lympho-node and 8 cases of organ metastasis.<elsevierMultimedia ident="tbl0001"></elsevierMultimedia>The association of CTCs number with the clinical characteristicsA total of 68 blood samples were collected before or after treatment, respectively. CTCs images are shown in <a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>. Based on the CTC surface mRNA markers, the CTCs were classified into three phenotypes: epithelial, mixed phenotypic, and mesenchymal CTCs. All 48 patients had obtained CTC assessment. The CTCs were detected in 34 of the 48 patients (70.8 %) with an average count of 6.76 CTCs (range 0‒17 per 5 mL blood). The results showed that there were 14 negative cases (29.2%) and 34 positive cases (70.8%). The authors also counted the total MCTCs, including MCTCs plus mixed CTCs cells, which account for 35.4% (17 cases). Their profiles are shown in <a class="elsevierStyleCrossRef" href="#fig0002">Fig. 2</a>. Compared with non-tumor control, total CTCs, epithelial CTCs (eCTCs), MCTCs, and mixed CTCs in CRC patients were significantly higher than in control cases. The authors compared negative and positive CTCs with gender, T-staging, N-staging, smoking history, and tumor locations of patients (<a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>). There were no significant differences among CTCs of patients in gender, smoking history, and tumor locations. However, CTCs positive cases in T3, T4, and above N2b staging were significantly higher than that in T2 and less N2b staging. These results indicated that there was a higher CTC positive rate in patients with CRC patients with advanced T-stages.<elsevierMultimedia ident="fig0001"></elsevierMultimedia><elsevierMultimedia ident="fig0002"></elsevierMultimedia><elsevierMultimedia ident="tbl0002"></elsevierMultimedia>Relationships between CTCs number and the outcomes of patients after treatmentTo investigate the roles of CTC numbers in the outcomes of CRC patients, the authors traced the patient's outcomes up to 30 months after treatments and recorded their PFS and OS times. PFS was defined as the time from treatment to the disease's progress. OS was defined as the time from treatments to the patient's death. The authors also compared the PFS and OS of patients using a cut-off value > 6 total CTCs or 5 MCTCs. The survival analysis was performed with Kaplan-Meier curves. The results are shown in <a class="elsevierStyleCrossRef" href="#fig0003">Fig. 3</a>. The authors found that when total CTCs were > 6 or MCTCs were > 5 MCTCs in 5 mL peripheral blood, PFS of the CRC patients in total > 6 CTCs or > 5 MCTCs group was significantly shorter than those patients with ≤ 6 CTCs or ≤ 5 MCTCs (p < 0.0001 and < 0.0001, Log-rank 4.543 and 4.066, respectively; <a class="elsevierStyleCrossRef" href="#fig0003">Fig. 3</a>A‒B). Similarly, when the presence of > 6 CTCs or > 5 MCTCs in 5 mL peripheral blood from patients was found, the OS of the CRC patients also displayed a poorer than those patients with ≤ 6 CTCs or ≤ 5 MCTCs (p < 0.0001 and p < 0.0001, Log-rank 5.318 and Log-rank 4.782, respectively; <a class="elsevierStyleCrossRef" href="#fig0003">Fig. 3</a>C‒D). These results revealed that CTCs monitored in the patients were a very useful biomarker for predicting the outcomes of CRC patients. Moreover, the number of metastatic lesions was also associated with progression-free survival, patients with > 1 metastatic lesion were found to exhibit a poorer PFS than those with ≤ 1 metastatic lesion. The authors investigated the prognostic potential of the changes in a number of CTC after treatment by Kaplan–Meier survival analyses for PFS and OS. The patients with ≥ 4 CTC number changed after treatment were found to exhibit a poorer PFS and OS than those with < 4 CTC number changed after treatments (data not shown). These results indicated that CTCs detection in CRC patients was a critical biomarker in predicting the prognosis of patients.<elsevierMultimedia ident="fig0003"></elsevierMultimedia>DiscussionRecently, applications of liquid biopsy techniques like CanPatrol™ CTC enrichment have greatly enhanced the clinical judgment of diagnosis, treatments, and outcomes.<a class="elsevierStyleCrossRefs" href="#bib0029">29–32</a> Liquid biopsy has many advantages over the traditional methods for precision medicine and early detection of diseases, including non-invasive ways and easily obtained samples like blood and urine. In the current study, the authors used CanPatrol™ CTC-enrichment and RNA-ISH assay to monitor CTCs changes in CRC patients. RNA-ISH assay has a few advantages over techniques for CTC detections: first, it can detect low to 10 copies of the target gene; second, RNA-ISH can accurately and precisely amplify the target gene by ∼10000‒10000000 fold;<a class="elsevierStyleCrossRef" href="#bib0028">28</a> third, RNA-ISH combined with a fluorescent microscope or flow cytometry to quantify target gene expression.<a class="elsevierStyleCrossRef" href="#bib0033">33</a>,<a class="elsevierStyleCrossRef" href="#bib0034">34</a> Recent literature have reported that CTC was strongly related to the progress, relapse, and metastasis of some cancers.<a class="elsevierStyleCrossRefs" href="#bib0035">35–37</a> CTCs have been recommended as a cancer hallmark by the American Society of Clinical Oncology for the ability to detect lesions in early stages in patients without cancer symptoms 2007.<a class="elsevierStyleCrossRef" href="#bib0038">38</a>,<a class="elsevierStyleCrossRef" href="#bib0039">39</a> Here, the present results confirmed that CTC can be used as a useful biomarker for the prognosis of tumors and explored the clinical significance of CTCs count in CRC patients.The present data showed that there were no significant differences between negative and positive CTCs in gender, smoking history, and tumor locations after treatment. However, the authors found that when numbers of total CTCs and MCTCs were higher than 6 or 5 in 5 mL peripheral blood, PFS and OS of the CRC patients were dramatically shorter than those patients with ≤ 6 CTCs or ≤ 5 MCTCs per 5 mL blood. The clinical significance of CTC in different cancer patients was extensively investigated<a class="elsevierStyleCrossRef" href="#bib0010">10</a>,<a class="elsevierStyleCrossRef" href="#bib0011">11</a>,<a class="elsevierStyleCrossRef" href="#bib0040">40</a>,<a class="elsevierStyleCrossRef" href="#bib0041">41</a> High CTC number was especially relevant to relapse and metastasis of advanced cancer patients, which are the major reasons for the high fatality rate. The mechanism of relapse and metastasis in cancer patients is very complex. The presence of CTCs is one of these reasons. The study showed that aberrant activation of the Epithelail-Mesenchymal Transition (EMT) of CTCs was the key mechanism of cancer metastasis.<a class="elsevierStyleCrossRef" href="#bib0042">42</a> The present data confirmed that total high CTCs and MCTCs in the CRC patients had shorter PFS and OS. This result indicated that CTC was a very useful biomarker for monitoring the progress of CRC patients.Previous studies revealed that CTC detection may help to assess the high-risk patient selection for adjuvant chemotherapy and guide the prognosis.<a class="elsevierStyleCrossRef" href="#bib0043">43</a>,<a class="elsevierStyleCrossRef" href="#bib0044">44</a> For the CRC patients, it was reported that Tumor-Derived Extracellular Vesicles (tdEV), Endothelium-Derived Extracellular Vesicles (edEVs), and CTCs detection were more powerful for predicting OS of the CRC patients.<a class="elsevierStyleCrossRef" href="#bib0045">45</a> Here, the authors found that the combination of total CTCs and MCTCs was a more effective t to monitoring the survival status of CRC patients than the alone number. In addition, the authors found that the sigmoid colon was the major site for the occurrence of CRC Cancer. However, the size of this study cohort was 48 patients and 20 control cases. This study size was limited. In addition, the follow-up time was 30 months, which limited PFS and OS times. Therefore, large size and longer time follow-up studies will be needed to confirm the current data.In conclusion, Total CTCs and MCTCs number detection of the CPC patients was a very useful biomarker for predicting the prognosis of patients; > 6 CTCs or 5 MCTCs in 5 mL peripheral blood had a shorter PFS and OS. Therefore, CTCs and MCTCs number detection provided a new therapeutic strategy for CRC patients.Ethics approval and informed consentThe study was approved by the ethics committee of the people's hospital of Guangxi Zhuang autonomous region (Approval n° KY-LW-2017-1). Written informed consent has obtained from all patients before the study. All procedures performed in the studies were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments or comparable ethical standards." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1953953" "titulo" => "HIGHLIGHTS" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abss0001" ] ] ] 1 => array:3 [ "identificador" => "xres1953954" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0003" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abss0004" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abss0005" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abss0006" "titulo" => "Conclusion" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1682064" "titulo" => "Keywords" ] 3 => array:2 [ "identificador" => "sec0001" "titulo" => "Introduction" ] 4 => array:3 [ "identificador" => "sec0002" "titulo" => "Materials and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0003" "titulo" => "Subjects and samples" ] 1 => array:2 [ "identificador" => "sec0004" "titulo" => "Isolation and identification of CTCs" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Tri-color RNA in situ hybridization assay" ] 3 => array:2 [ "identificador" => "sec0006" "titulo" => "Statistical analysis" ] ] ] 5 => array:3 [ "identificador" => "sec0007" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0008" "titulo" => "Patients and CTC characteristics" ] 1 => array:2 [ "identificador" => "sec0009" "titulo" => "The association of CTCs number with the clinical characteristics" ] 2 => array:2 [ "identificador" => "sec0010" "titulo" => "Relationships between CTCs number and the outcomes of patients after treatment" ] ] ] 6 => array:3 [ "identificador" => "sec0011" "titulo" => "Discussion" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0012" "titulo" => "Ethics approval and informed consent" ] ] ] 7 => array:1 [ "titulo" => "Reference" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-01-15" "fechaAceptado" => "2022-04-04" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1682064" "palabras" => array:5 [ 0 => "Colon cancer" 1 => "Circulating tumour cells" 2 => "Relapse" 3 => "Metastasis" 4 => "Overall survival" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundRelapse and metastasis of patients with Colorectal Cancer (CRC) is the major obstacle to the long-term life of patients. Its mechanisms remain defined. MethodsA total of 48 CRC patients were enrolled and 68 samples were obtained from the peripheral blood of patients before or after treatments in this study. Twenty non-cancer patients were also detected as a negative control. Circulating Tumor Cells (CTCs), including Epithelial CTCs (eCTCs), Mesenchymal (MCTCs), and epithelial/mesenchymal mixed phenotypes (mixed CTCs), were identified by CanPatrolTM CTC enrichment and RNA in situ hybridization. The relationship between CTCs number and Progression-Free Survival (PFS) or Overall Survival (OS) was evaluated. ResultsThirty-four of 48 patients (70.8%) were found to have positive CTCs. Total CTCs and MCTCs in the post-treatment had a significant correlation PFS and OS. When total CTCs or MCTCs in 5 mL blood of patients were more than 6 CTCs or 5 MCTCs, PFS of the patients was significantly shorter (p < 0.05) than that in patients with less than 6 CTCs or 5 MCTCs. The patients with > 5 CTCs count changes were found to exhibit poor PFS and OS rates (p < 0.05). ConclusionTotal CTCs and MCTCs number detection in patients with colorectal cancer was very useful biomarker for predicting the prognosis of patients. Higher CTCs or MCTCs had poorer PFS and OS rates." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0003" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abss0004" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abss0005" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abss0006" "titulo" => "Conclusion" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "Equal contribution" "identificador" => "fn1" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0001" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2347 "Ancho" => 1583 "Tamanyo" => 186555 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Images of CTCs. Up, middle, and low panels show the pictures of epithelial, mesenchymal,and mixed CTCs. Epithelial CTCs were stained with only Alexa Fluor 594 labeled epithelial markers EpCAM and CK8/18/19. Mesenchymal CTCs were stained with Alexa Fluor 488 labeled Vimentin and Twist. Pictures were taken by 40 ×  magnification in immunofluorescence microscope." ] ] 1 => array:8 [ "identificador" => "fig0002" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1830 "Ancho" => 1708 "Tamanyo" => 120596 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0002" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Comparsion of CTCs and subtypes in CRC patients and control patients. (A) Total CTC number comparison; (B) Epithelial CTC number comparison; (C) Mixed CTC number comparison; (D) MCTC number comparison. CTCs, Circulating Tumor Cells; MCTC, Mesenchyal Circulating Tumor Cell." ] ] 2 => array:8 [ "identificador" => "fig0003" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2032 "Ancho" => 3583 "Tamanyo" => 289154 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0003" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "PFS of patients with CTCs and MCTC by Kaplan-Meier curves at diagnosis. (A) PFS in > 6 CTCs vs. ≤ 6 CTCs of CRC patients; (B) PFS in > 5 MCTCs vs. ≤ 5 MCTCs of CRC patients; (C) Comparison of OS > 6 CTCs vs. ≤ 6 CTCs of CRC patients; (D) Comparison of OS > 5 MCTCs vs. ≤5 MCTCs of CRC patients. CTCs, Circulating Tumor Cells; MCTC, Mesenchyal Circulating Tumor Cell; PFS, Progression-Free Survival; OS, Overall Durvival." ] ] 3 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0004" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">Patients number \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0005"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">Control number \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><a name="en0006"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0007"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">NO \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0008"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0009"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">NO \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0010"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0011"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Age (Year-old) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0013"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0016"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Mean \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">52.42 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">47.5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Range \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22‒80 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">32‒74 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0026"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Gender \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0031"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0036"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0041"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Tumor Location \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0046"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cecum \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">6.3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0049"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="5" align="left" valign="top">N/A</td><a name="en0050"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="5" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0051"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Ascending colon \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">14.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0056"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Transverse colon \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Decending colon \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0066"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Sigmoid colon \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">58.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0071"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Stage \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0076"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">58.3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0079"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">N/A</td><a name="en0080"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0081"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0086"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IV \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0091"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Differentiation \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0095"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0096"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Low \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0099"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">N/A</td><a name="en0100"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0101"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0103"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">73 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0106"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Well \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0111"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Metastasis \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0113"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0115"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0116"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Lymphonode \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">27.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0119"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top"></td><a name="en0120"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0121"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Organ \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0123"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">14.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3252577.png" ] ] ] ] "descripcion" => array:1 [ "en" => "The clinical Characteristics of colorectal patients and controls." ] ] 4 => array:8 [ "identificador" => "tbl0002" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "CTCs, Circulating Tumor Cells; n, Case number." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0126"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Variants \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0127"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">0 CTC (%)(n = 14) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0128"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">≥ 1 CTC (%)(n = 34) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0129"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0130"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Gender \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0131"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0133"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">15 (31.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0134"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0135"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7 (14.6) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0136"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">19 (39.4) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0137"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">0.758 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0138"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7 (14.6) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0140"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0141"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0142"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">T-staging \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0143"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0144"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0145"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0146"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">T2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">12 (25) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0148"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0149"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0150"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">T3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0151"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0152"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 (20.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0154"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">T4 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0155"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 (0.0) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0156"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0158"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N staging \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0159"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0160"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0161"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0162"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">< N2b \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0163"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">13 (27.1) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0164"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 (20.8) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0165"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0166"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">≥ N2b \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0167"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0168"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">23 (47.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0170"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Smoking History \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0171"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0172"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0173"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">0.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0174"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Smoking \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0175"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4(8.3) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0176"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4(8.3) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0177"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0178"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Non-smoking \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0179"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 (20.9) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0180"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30 (62.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0182"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Tumor location \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0183"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0184"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0185"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">0.89 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0186"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cecum \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0187"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 (2.1) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0188"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0189"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="5" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0190"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Ascending Colon \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0191"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0192"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">5 (10.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0194"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Transverse Colon \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0195"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0196"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">3 (6.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0198"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Decending Colon \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0199"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0200"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">3 (6.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0202"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Sigmoid Colon \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0203"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7 (14.6) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0204"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21 (43.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3252576.png" ] ] ] ] "descripcion" => array:1 [ "en" => "The clinical parameters associated with baseline CTCs in the CRC patients before treatments (Fisher's exact test and Pearson Chi-Square test)." ] ] ] "bibliografia" => array:2 [ "titulo" => "Reference" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec1" "bibliografiaReferencia" => array:45 [ 0 => array:3 [ "identificador" => "bib0001" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J Ferlay" 1 => "I Soerjomataram" 2 => "R Dikshit" 3 => "S Eser" 4 => "C Mathers" 5 => "M Rebelo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ijc.29210" "Revista" => array:7 [ "tituloSerie" => "Int J Cancer" "fecha" => "2015" "volumen" => "136" "numero" => "5" "paginaInicial" => "E359" "paginaFinal" => "E386" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25220842" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0002" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "MB Amin" 1 => "FL Greene" 2 => "SB Edge" 3 => "CC Compton" 4 => "JE Gershenwald" 5 => "RK Brookland" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3322/caac.21388" "Revista" => array:7 [ "tituloSerie" => "CA Cancer J Clin" "fecha" => "2017" "volumen" => "67" "numero" => "2" "paginaInicial" => "93" "paginaFinal" => "99" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28094848" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0003" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Colon cancer: a civilization disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "AJ Watson" 1 => "PD. 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Kehe Chen1, Zhenxiang Chen1, Mei Ou, Junping Wang, Xiao Huang, Yingying Wu, Wenhe Zhong, Jiao Yang, Jinging Huang, Min Huang, Deng Pan

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pandeng@163.com

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Department of Medical Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China

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          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Comparsion of CTCs and subtypes in CRC patients and control patients&#46; &#40;A&#41; Total CTC number comparison&#59; &#40;B&#41; Epithelial CTC number comparison&#59; &#40;C&#41; Mixed CTC number comparison&#59; &#40;D&#41; MCTC number comparison&#46; CTCs&#44; Circulating Tumor Cells&#59; MCTC&#44; Mesenchyal Circulating Tumor Cell&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Introduction</span><p id="para0009" class="elsevierStylePara elsevierViewall">Worldwide&#44; Colorectal Cancer &#40;CRC&#41; is the fourth most lethal cancer after lung&#44; stomach&#44; and liver cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> Its incidence ranks second cancer in women and third cancer in men&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> Bad eating habits&#44; smoking&#44; insufficient physical exercise&#44; and obesity are the most common risk factors for the occurrence of CRC&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> In addition&#44; the patients with hereditary nonpolyposis colorectal cancer &#40;HNPCC<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> or Lynch syndrome&#41; and inflammatory bowel disease<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> also have a risk for this disease&#46; CRC treatments include surgery&#44; chemotherapy&#44; radiotherapy&#44; and immunotherapy&#44; which are very useful for those patients with mismatch repair deficiency and microsatellite instability&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a></p><p id="para0010" class="elsevierStylePara elsevierViewall">Although diagnosis and treatments of CRC had great progress in the past decades&#44; its long-term survival rate is less than&#160;60&#37; or more low&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> The survival rate of CRC is directly related to the types and Tumor-Node-Metastasis &#40;TNM stages&#41; of CRC&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> In addition&#44; the survival rate of CRC is also linked to specific gene expressions such as HSPA1A and RBM3&#46;<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> Recent studies revealed that the presence of Circulation Tumor Cells &#40;CTCs&#41; in cancer patients was closely associated with the relapse and metastasis of cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">10&#8211;12</span></a> CTCs are cells originally from a primary tumor and can become seeds for tumor growth in distant organs by blood circulation system&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> This mechanism was the reason for the recurrence and metastasis of many cancers such as breast cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> lung cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a> gastric cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0017"><span class="elsevierStyleSup">17</span></a> head and neck cancers&#44;<a class="elsevierStyleCrossRefs" href="#bib0018"><span class="elsevierStyleSup">18&#8211;20</span></a> as well as resistance to anti-cancer treatment&#46;</p><p id="para0011" class="elsevierStylePara elsevierViewall">In contrast&#44; CTC-based liquid biopsies have a few advantages over traditional method&#46;<a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> First&#44; it is a non-invasive and repeatable technique for monitoring metastasis&#44; progress&#44; and therapeutic efficiency of cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> Second&#44; cell resources are from the peripheral blood of the patients and are easily obtained in the solid tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> Third&#44; the CTC detections of solid tumors avoid surgery for evaluating metastasis of cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> Therefore&#44; monitoring changes of CTCs in cancer patients have a great clinical value in assessing diagnosis&#44; therapy&#44; relapse&#44; metastasis&#44; and prognosis of cancer patients&#46; In our study&#44; the authors aim to investigate the correlation between CTCs profiles and the clinical features of CRC&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Materials and methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Subjects and samples</span><p id="para0012" class="elsevierStylePara elsevierViewall">A total of&#160;48&#160;CRC and 20&#160;patients without tumors as a control were enrolled in this study from January&#160;2018 to October&#160;2020&#46; The diagnosis of these patients was confirmed by pathological and radiological findings from surgery or biopsy samples&#46; TNM staging system for CRC patients followed the criteria of the American Joint Committee on Cancer &#40;AJCC&#41; 8th&#160;edition&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> Those patients outside of the studied hospital or without tumor tissue available were excluded from this study&#46; All participants also must meet the following criteria&#58; no active infection and normal liver&#44; kidney&#44; and cardiology functions&#46; A total of&#160;5&#160;milliliters &#40;mL&#41; of whole blood samples from patients were collected before or after treatments&#46; All clinical characteristics of patients were documented and identified&#46; All patients also followed up for their PFS and Overall Survival &#40;OS&#41;&#46; PFS was calculated as the time from the initial treatment to disease progression&#46; OS is the time from the initial treatment to death&#46; Tumor burden were counted using clinical and imaging data like Computer Tomography &#40;CT&#41; or Magnetic Resonance Imaging &#40;MRI&#41;&#46;</p><p id="para0013" class="elsevierStylePara elsevierViewall">The study protocol was reviewed and approved by the ethics committee of the people&#39;s hospital of Guangxi Zhuang autonomous region&#46; Written informed consent has obtained from all patients before the study&#46; All procedures performed in the studies were in accordance with the ethical standards of the&#160;1964 Helsinki declaration and its later amendments or comparable ethical standards&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Isolation and identification of CTCs</span><p id="para0014" class="elsevierStylePara elsevierViewall">A filtration method was applied to isolate and identify CTCs following the previous technique&#46;<a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a> Briefly&#44; blood samples were collected before and after treatment&#46; Red blood cells were removed using a red blood cell lysis buffer &#40;154&#160;mM NH<span class="elsevierStyleInf">4</span>Cl&#44; 10&#160;mM KHCO<span class="elsevierStyleInf">3&#44;</span> and 0&#46;1&#160;mM EDTA&#41; and incubated for&#160;30&#160;minutes at room temperature&#46; The remaining cells were fixed containing&#160;4&#37; formaldehyde &#40;Sigma&#44; St&#46; Louis&#44; USA&#41; with <span class="elsevierStyleItalic">Phosphate Buffered Saline &#40;</span>PBS&#41; solution for&#160;5&#160;minutes&#46; Then the cells were transferred to the filtration tube with an&#160;8&#160;&#956;M pore size filter membrane for the manifold vacuum plate and started to filtrate CTCs&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Tri-color RNA in situ hybridization assay</span><p id="para0015" class="elsevierStylePara elsevierViewall">The RNA-in situ hybridization<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> technique based on the branched DNA &#40;bDNA&#41; signal amplification system<a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a> was applied to characterize CTCs&#46; Briefly&#44; bDNA capture probe is used to bind&#160;&#62; 30&#160;specific nucleotide sequences called Label Extenders &#40;LEs&#41; of an interested gene&#44; which LE probes bind preamplifiers&#46; In turn&#44; preamplifiers bind many amplifiers and the label probe&#44; which are the Alexa Fluor&#160;594&#160;conjugated epithelial biomarkers EpCAM and CK8&#47;18&#47;19&#44; Alexa Fluor&#160;488 conjugated mesenchymal biomarkers vimentin and twist&#44; and 4&#8242;&#44;6-Diamidino-2-Phenylindole&#160;9 &#40;DAPI&#41; staining&#46; The results are that low up to&#160;10&#160;copies of original specific gene sequences can be accurately amplified between &#8764;10&#44;000 and 10&#44;000&#44;000&#160;fold&#46; In addition&#44; these fluorescents labeled antibodies are easily observed and counted in a fluorescent microscope&#46;</p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">Statistical analysis</span><p id="para0016" class="elsevierStylePara elsevierViewall">Data were analyzed using statistic analyzing Excel and GraphPad Prism8 software&#46; The &#967;2 test&#44; <span class="elsevierStyleItalic">t</span>-test&#44; and Kaplan-Meier analysis were performed to analyze the data&#59; p &#60; 0&#46;05 was considered a significant difference&#46;</p></span></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Results</span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">Patients and CTC characteristics</span><p id="para0017" class="elsevierStylePara elsevierViewall">A total of&#160;48&#160;CRC patients and 20&#160;free-tumor control patients were recruited for this study&#46; The detailed patient characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0001">Table&#160;1</a>&#46; Their average age was&#160;52&#46;42&#160;years old and the range was from&#160;20&#8210;80&#160;years old&#44; including&#160;26&#160;males and 22&#160;females&#46; The number of patients from the cecum&#44; ascending colon&#44; transverse colon&#44; descending colon&#44; and sigmoid colon were 3&#44; 7&#44; 5&#44; 5&#44; and 28&#44; respectively&#46; Stage&#160;II&#44;&#160;III&#44; and&#160;IV patient numbers were 28&#44; 12&#44; and 8&#44; respectively&#46; Low&#44; moderate&#44; and well differentiation patients were 6&#44; 35&#44; and 7&#44; respectively&#46; Twenty patients had metastatic disease&#44; including&#160;13&#160;cases of lympho-node and 8&#160;cases of organ metastasis&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">The association of CTCs number with the clinical characteristics</span><p id="para0018" class="elsevierStylePara elsevierViewall">A total&#160;of 68&#160;blood samples were collected before or after treatment&#44; respectively&#46; CTCs images are shown in <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46;&#160;1</a>&#46; Based on the CTC surface mRNA markers&#44; the CTCs were classified into three phenotypes&#58; epithelial&#44; mixed phenotypic&#44; and mesenchymal CTCs&#46; All&#160;48&#160;patients had obtained CTC assessment&#46; The CTCs were detected in&#160;34 of the&#160;48&#160;patients &#40;70&#46;8 &#37;&#41; with an average count of&#160;6&#46;76&#160;CTCs &#40;range 0&#8210;17&#160;per&#160;5&#160;mL blood&#41;&#46; The results showed that there were&#160;14&#160;negative cases &#40;29&#46;2&#37;&#41; and 34&#160;positive cases &#40;70&#46;8&#37;&#41;&#46; The authors also counted the total MCTCs&#44; including MCTCs plus mixed CTCs cells&#44; which account for&#160;35&#46;4&#37; &#40;17&#160;cases&#41;&#46; Their profiles are shown in <a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46;&#160;2</a>&#46; Compared with non-tumor control&#44; total CTCs&#44; epithelial CTCs &#40;eCTCs&#41;&#44; MCTCs&#44; and mixed CTCs in CRC patients were significantly higher than in control cases&#46; The authors compared negative and positive CTCs with gender&#44; T-staging&#44; N-staging&#44; smoking history&#44; and tumor locations of patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0002">Table&#160;2</a>&#41;&#46; There were no significant differences among CTCs of patients in gender&#44; smoking history&#44; and tumor locations&#46; However&#44; CTCs positive cases in T3&#44; T4&#44; and above N2b staging were significantly higher than that in T2 and less N2b staging&#46; These results indicated that there was a higher CTC positive rate in patients with CRC patients with advanced T-stages&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><elsevierMultimedia ident="fig0002"></elsevierMultimedia><elsevierMultimedia ident="tbl0002"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">Relationships between CTCs number and the outcomes of patients after treatment</span><p id="para0019" class="elsevierStylePara elsevierViewall">To investigate the roles of CTC numbers in the outcomes of CRC patients&#44; the authors traced the patient&#39;s outcomes up to&#160;30&#160;months after treatments and recorded their PFS and OS times&#46; PFS was defined as the time from treatment to the disease&#39;s progress&#46; OS was defined as the time from treatments to the patient&#39;s death&#46; The authors also compared the PFS and OS of patients using a cut-off value&#160;&#62; 6&#160;total CTCs or&#160;5&#160;MCTCs&#46; The survival analysis was performed with Kaplan-Meier curves&#46; The results are shown in <a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46;&#160;3</a>&#46; The authors found that when total CTCs were&#160;&#62; 6&#160;or&#160;MCTCs were&#160;&#62;&#160;5&#160;MCTCs in&#160;5&#160;mL peripheral blood&#44; PFS of the CRC patients in total&#160;&#62; 6&#160;CTCs&#160;or&#160;&#62; 5&#160;MCTCs group was significantly shorter than those patients with&#160;&#8804; 6&#160;CTCs&#160;or&#160;&#8804; 5&#160;MCTCs &#40;p &#60; 0&#46;0001 and &#60; 0&#46;0001&#44; Log-rank&#160;4&#46;543 and 4&#46;066&#44; respectively&#59; <a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46;&#160;3</a>A&#8210;B&#41;&#46; Similarly&#44; when the presence of&#160;&#62; 6&#160;CTCs&#160;or&#160;&#62; 5&#160;MCTCs in&#160;5&#160;mL peripheral blood from patients was found&#44; the OS of the CRC patients also displayed a poorer than those patients with&#160;&#8804; 6&#160;CTCs&#160;or&#160;&#8804; 5&#160;MCTCs &#40;p &#60; 0&#46;0001 and p &#60; 0&#46;0001&#44; Log-rank&#160;5&#46;318 and Log-rank&#160;4&#46;782&#44; respectively&#59; <a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46;&#160;3</a>C&#8210;D&#41;&#46; These results revealed that CTCs monitored in the patients were a very useful biomarker for predicting the outcomes of CRC patients&#46; Moreover&#44; the number of metastatic lesions was also associated with progression-free survival&#44; patients with&#160;&#62; 1&#160;metastatic lesion were found to exhibit a poorer PFS than those with&#160;&#8804; 1&#160;metastatic lesion&#46; The authors investigated the prognostic potential of the changes in a number of CTC after treatment by Kaplan&#8211;Meier survival analyses for PFS and OS&#46; The patients with&#160;&#8805; 4&#160;CTC number changed after treatment were found to exhibit a poorer PFS and OS than those with&#160;&#60; 4&#160;CTC number changed after treatments &#40;data not shown&#41;&#46; These results indicated that CTCs detection in CRC patients was a critical biomarker in predicting the prognosis of patients&#46;</p><elsevierMultimedia ident="fig0003"></elsevierMultimedia></span></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">Discussion</span><p id="para0020" class="elsevierStylePara elsevierViewall">Recently&#44; applications of liquid biopsy techniques like CanPatrol&#8482; CTC enrichment have greatly enhanced the clinical judgment of diagnosis&#44; treatments&#44; and outcomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0029"><span class="elsevierStyleSup">29&#8211;32</span></a> Liquid biopsy has many advantages over the traditional methods for precision medicine and early detection of diseases&#44; including non-invasive ways and easily obtained samples like blood and urine&#46; In the current study&#44; the authors used CanPatrol&#8482; CTC-enrichment and RNA-ISH assay to monitor CTCs changes in CRC patients&#46; RNA-ISH assay has a few advantages over techniques for CTC detections&#58; first&#44; it can detect low to&#160;10&#160;copies of the target gene&#59; second&#44; RNA-ISH can accurately and precisely amplify the target gene by &#8764;10000&#8210;10000000&#160;fold&#59;<a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a> third&#44; RNA-ISH combined with a fluorescent microscope or flow cytometry to quantify target gene expression&#46;<a class="elsevierStyleCrossRef" href="#bib0033"><span class="elsevierStyleSup">33</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0034"><span class="elsevierStyleSup">34</span></a> Recent literature have reported that CTC was strongly related to the progress&#44; relapse&#44; and metastasis of some cancers&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">35&#8211;37</span></a> CTCs have been recommended as a cancer hallmark by the American Society of Clinical Oncology for the ability to detect lesions in early stages in patients without cancer symptoms&#160;2007&#46;<a class="elsevierStyleCrossRef" href="#bib0038"><span class="elsevierStyleSup">38</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0039"><span class="elsevierStyleSup">39</span></a> Here&#44; the present results confirmed that CTC can be used as a useful biomarker for the prognosis of tumors and explored the clinical significance of CTCs count in CRC patients&#46;</p><p id="para0021" class="elsevierStylePara elsevierViewall">The present data showed that there were no significant differences between negative and positive CTCs in gender&#44; smoking history&#44; and tumor locations after treatment&#46; However&#44; the authors found that when numbers of total CTCs and MCTCs were higher than&#160;6&#160;or&#160;5 in&#160;5&#160;mL peripheral blood&#44; PFS and OS of the CRC patients were dramatically shorter than those patients with&#160;&#8804; 6&#160;CTCs&#160;or&#160;&#8804; 5&#160;MCTCs per&#160;5&#160;mL blood&#46; The clinical significance of CTC in different cancer patients was extensively investigated<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">40</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0041"><span class="elsevierStyleSup">41</span></a> High CTC number was especially relevant to relapse and metastasis of advanced cancer patients&#44; which are the major reasons for the high fatality rate&#46; The mechanism of relapse and metastasis in cancer patients is very complex&#46; The presence of CTCs is one of these reasons&#46; The study showed that aberrant activation of the Epithelail-Mesenchymal Transition &#40;EMT&#41; of CTCs was the key mechanism of cancer metastasis&#46;<a class="elsevierStyleCrossRef" href="#bib0042"><span class="elsevierStyleSup">42</span></a> The present data confirmed that total high CTCs and MCTCs in the CRC patients had shorter PFS and OS&#46; This result indicated that CTC was a very useful biomarker for monitoring the progress of CRC patients&#46;</p><p id="para0022" class="elsevierStylePara elsevierViewall">Previous studies revealed that CTC detection may help to assess the high-risk patient selection for adjuvant chemotherapy and guide the prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0043"><span class="elsevierStyleSup">43</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0044"><span class="elsevierStyleSup">44</span></a> For the CRC patients&#44; it was reported that Tumor-Derived Extracellular Vesicles &#40;tdEV&#41;&#44; Endothelium-Derived Extracellular Vesicles &#40;edEVs&#41;&#44; and CTCs detection were more powerful for predicting OS of the CRC patients&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">45</span></a> Here&#44; the authors found that the combination of total CTCs and MCTCs was a more effective t to monitoring the survival status of CRC patients than the alone number&#46; In addition&#44; the authors found that the sigmoid colon was the major site for the occurrence of CRC Cancer&#46; However&#44; the size of this study cohort was&#160;48&#160;patients and 20&#160;control cases&#46; This study size was limited&#46; In addition&#44; the follow-up time was&#160;30&#160;months&#44; which limited PFS and OS times&#46; Therefore&#44; large size and longer time follow-up studies will be needed to confirm the current data&#46;</p><p id="para0023" class="elsevierStylePara elsevierViewall">In conclusion&#44; Total CTCs and MCTCs number detection of the CPC patients was a very useful biomarker for predicting the prognosis of patients&#59; &#62; 6&#160;CTCs&#160;or&#160;5&#160;MCTCs in&#160;5&#160;mL peripheral blood had a shorter PFS and OS&#46; Therefore&#44; CTCs and MCTCs number detection provided a new therapeutic strategy for CRC patients&#46;</p><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">Ethics approval and informed consent</span><p id="para0024" class="elsevierStylePara elsevierViewall">The study was approved by the ethics committee of the people&#39;s hospital of Guangxi Zhuang autonomous region &#40;Approval n&#176;&#160;KY-LW-2017-1&#41;&#46; Written informed consent has obtained from all patients before the study&#46; All procedures performed in the studies were in accordance with the ethical standards of the&#160;1964 Helsinki declaration and its later amendments or comparable ethical standards&#46;</p></span></span></span>"
    "textoCompletoSecciones" => array:1 [
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          "identificador" => "xres1953954"
          "titulo" => "Abstract"
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              "titulo" => "Background"
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            1 => array:2 [
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        2 => array:2 [
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          "titulo" => "Keywords"
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        3 => array:2 [
          "identificador" => "sec0001"
          "titulo" => "Introduction"
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        4 => array:3 [
          "identificador" => "sec0002"
          "titulo" => "Materials and methods"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0003"
              "titulo" => "Subjects and samples"
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            1 => array:2 [
              "identificador" => "sec0004"
              "titulo" => "Isolation and identification of CTCs"
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            2 => array:2 [
              "identificador" => "sec0005"
              "titulo" => "Tri-color RNA in situ hybridization assay"
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          "titulo" => "Results"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0008"
              "titulo" => "Patients and CTC characteristics"
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            1 => array:2 [
              "identificador" => "sec0009"
              "titulo" => "The association of CTCs number with the clinical characteristics"
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            2 => array:2 [
              "identificador" => "sec0010"
              "titulo" => "Relationships between CTCs number and the outcomes of patients after treatment"
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          "titulo" => "Discussion"
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              "titulo" => "Ethics approval and informed consent"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2022-01-15"
    "fechaAceptado" => "2022-04-04"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1682064"
          "palabras" => array:5 [
            0 => "Colon cancer"
            1 => "Circulating tumour cells"
            2 => "Relapse"
            3 => "Metastasis"
            4 => "Overall survival"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Background</span><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">Relapse and metastasis of patients with Colorectal Cancer &#40;CRC&#41; is the major obstacle to the long-term life of patients&#46; Its mechanisms remain defined&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Methods</span><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">A total of&#160;48&#160;CRC patients were enrolled and 68&#160;samples were obtained from the peripheral blood of patients before or after treatments in this study&#46; Twenty non-cancer patients were also detected as a negative control&#46; Circulating Tumor Cells &#40;CTCs&#41;&#44; including Epithelial CTCs &#40;eCTCs&#41;&#44; Mesenchymal &#40;MCTCs&#41;&#44; and epithelial&#47;mesenchymal mixed phenotypes &#40;mixed CTCs&#41;&#44; were identified by CanPatrol<span class="elsevierStyleSup">TM</span> CTC enrichment and RNA in situ hybridization&#46; The relationship between CTCs number and Progression-Free Survival &#40;PFS&#41; or Overall Survival &#40;OS&#41; was evaluated&#46;</p></span> <span id="abss0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Results</span><p id="spara010" class="elsevierStyleSimplePara elsevierViewall">Thirty-four of&#160;48&#160;patients &#40;70&#46;8&#37;&#41; were found to have positive CTCs&#46; Total CTCs and MCTCs in the post-treatment had a significant correlation PFS and OS&#46; When total CTCs or MCTCs in&#160;5&#160;mL blood of patients were more than&#160;6&#160;CTCs or 5&#160;MCTCs&#44; PFS of the patients was significantly shorter &#40;p &#60; 0&#46;05&#41; than that in patients with less than&#160;6&#160;CTCs&#160;or&#160;5&#160;MCTCs&#46; The patients with&#160;&#62; 5&#160;CTCs count changes were found to exhibit poor PFS and OS rates &#40;p &#60; 0&#46;05&#41;&#46;</p></span> <span id="abss0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0006">Conclusion</span><p id="spara011" class="elsevierStyleSimplePara elsevierViewall">Total CTCs and MCTCs number detection in patients with colorectal cancer was very useful biomarker for predicting the prognosis of patients&#46; Higher CTCs or MCTCs had poorer PFS and OS rates&#46;</p></span>"
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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Images of CTCs&#46; Up&#44; middle&#44; and low panels show the pictures of epithelial&#44; mesenchymal&#44;and mixed CTCs&#46; Epithelial CTCs were stained with only Alexa Fluor&#160;594 labeled epithelial markers EpCAM and CK8&#47;18&#47;19&#46; Mesenchymal CTCs were stained with Alexa Fluor&#160;488 labeled Vimentin and Twist&#46; Pictures were taken by&#160;40&#160;&#215;&#160;&#160;magnification in immunofluorescence microscope&#46;</p>"
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          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Comparsion of CTCs and subtypes in CRC patients and control patients&#46; &#40;A&#41; Total CTC number comparison&#59; &#40;B&#41; Epithelial CTC number comparison&#59; &#40;C&#41; Mixed CTC number comparison&#59; &#40;D&#41; MCTC number comparison&#46; CTCs&#44; Circulating Tumor Cells&#59; MCTC&#44; Mesenchyal Circulating Tumor Cell&#46;</p>"
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          "en" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">PFS of patients with CTCs and MCTC by Kaplan-Meier curves at diagnosis&#46; &#40;A&#41; PFS in&#160;&#62; 6&#160;CTCs&#160;vs&#46;&#160;&#8804;&#160;6&#160;CTCs of CRC patients&#59; &#40;B&#41; PFS in&#160;&#62; 5&#160;MCTCs&#160;vs&#46;&#160;&#8804;&#160;5&#160;MCTCs of CRC patients&#59; &#40;C&#41; Comparison of OS&#160;&#62; 6&#160;CTCs&#160;vs&#46;&#160;&#8804;&#160;6&#160;CTCs of CRC patients&#59; &#40;D&#41; Comparison of OS&#160;&#62; 5&#160;MCTCs vs&#46;&#160;&#8804;5&#160;MCTCs of CRC patients&#46; CTCs&#44; Circulating Tumor Cells&#59; MCTC&#44; Mesenchyal Circulating Tumor Cell&#59; PFS&#44; Progression-Free Survival&#59; OS&#44; Overall Durvival&#46;</p>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Age &#40;Year-old&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Range&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">22&#8210;80&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">46&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0041"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Tumor Location&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0046"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cecum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="5" align="left" valign="top">N&#47;A</td><a name="en0050"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="5" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0051"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Ascending colon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0056"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Transverse colon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Decending colon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0066"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Sigmoid colon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">58&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0071"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Stage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0076"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">58&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0079"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">N&#47;A</td><a name="en0080"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0081"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">25&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0086"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0091"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Differentiation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0095"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0096"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Low&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0099"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top">N&#47;A</td><a name="en0100"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0101"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0103"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0106"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Well&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0111"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Metastasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0113"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0115"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0116"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Lymphonode&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">27&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0119"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top"></td><a name="en0120"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top"></td></tr><tr title="table-row"><a name="en0121"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Organ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0123"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3252577.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara004" class="elsevierStyleSimplePara elsevierViewall">The clinical Characteristics of colorectal patients and controls&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0002"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0005"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spara006" class="elsevierStyleSimplePara elsevierViewall">CTCs&#44; Circulating Tumor Cells&#59; n&#44; Case number&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0126"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">Variants</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0127"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">0 CTC &#40;&#37;&#41;&#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;14&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0128"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">&#8805; 1 CTC &#40;&#37;&#41;&#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;34&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0129"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">p</span>-value</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0130"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0131"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0133"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">15 &#40;31&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0134"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0135"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7 &#40;14&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0136"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19 &#40;39&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0137"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">0&#46;758&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0138"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7 &#40;14&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0140"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0141"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">T-staging&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">T2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="" valign="top">10 &#40;20&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">T4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0155"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">N staging&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0159"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top">0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0162"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">&#60; N2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0163"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13 &#40;27&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">10 &#40;20&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0165"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="" valign="top">&#8805; N2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0167"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0168"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">23 &#40;47&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0170"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Smoking History&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0171"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><a name="en0173"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">0&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0174"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Smoking&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="" valign="top">Non-smoking&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0182"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">Tumor location&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">1 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">2 &#40;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;6&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7 &#40;14&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0204"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">21 &#40;43&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spara005" class="elsevierStyleSimplePara elsevierViewall">The clinical parameters associated with baseline CTCs in the CRC patients before treatments &#40;Fisher&#39;s exact test and Pearson Chi-Square test&#41;&#46;</p>"
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Article information

ISSN: 18075932
Original language: English

DOI:10.1016/j.clinsp.2022.100070

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Year/Month	Html	Pdf	Total

2024 October	29	25	54
2024 September	71	46	117
2024 August	64	26	90
2024 July	55	16	71
2024 June	50	13	63
2024 May	46	24	70
2024 April	46	27	73
2024 March	91	23	114
2024 February	73	26	99
2024 January	76	23	99
2023 December	72	45	117
2023 November	93	42	135
2023 October	79	37	116
2023 September	70	32	102
2023 August	60	12	72
2023 July	51	28	79
2023 June	43	20	63
2023 May	81	15	96
2023 April	35	3	38
2023 March	16	6	22
2023 February	6	16	22
2023 January	19	6	25
2022 December	36	17	53
2022 November	0	0	0

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