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Analysis of PD-1/PD-L1 variations in lung cancer and association with immunotherapeutic efficacy and prognosis: A nonrandomized controlled trial
Jun Maa,
Corresponding author
majun2008@gzhmu-edu.cn

Corresponding author.
, JianRui Songb, LiNa Hanc, Wen Zhoua, LiFeng Menga, JianHui Lia, XiaoMing Baia
a Department of Thoracic Surgery, Shanxi Provincial People's Hospital, Shuangta Temple Street, Taiyuan City, Shanxi Province, China
b Wisdom Lake Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou City, Jiangsu Province, China
c Office of Health Emergency, Shanxi Provincial People's Hospital, Fifth Clinical Medical College, Shanxi Medical University, Taiyuan City, Shanxi Province, China
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Introduction</span><p id="para0008" class="elsevierStylePara elsevierViewall">Lung Cancer &#40;LC&#41;&#44; the malignant tumor with the most elevated morbidity and mortality in China&#44; is severely invasive and numerous patients are already in the advanced stage at the time of diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> Surgery&#44; chemotherapy and radiotherapy&#44; the crucial strategies for LC&#39;s cure&#44; are available to imperatively alleviate patients&#8217; clinical symptoms and ameliorate their quality of life&#44; while patients&#8217; prognosis is still unpleasing&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a></p><p id="para0009" class="elsevierStylePara elsevierViewall">Research has manifested that immunotherapy is available to distinctly prolong patients&#8217; survival period&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> Immunotherapy strengthens immune cell function via immunosuppressants to block the co-suppression pathway&#44; ultimately enhancing tumor cells&#8217; killing ability&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> Recently&#44; immunotherapy with Programmed Death Receptor-1 &#40;PD-1&#41; and Programmed Death Ligand-1 &#40;PD-L1&#41; as checkpoints have been broadly adopted in LC&#39;s clinical treatment&#46; PD-1&#44; immunoglobulin superfamily type I transmembrane glycoprotein composed of 288 amino acids&#44; is crucially expressed on activated T-cells&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> PD-L1 appertains to PD-1&#8242;s ligands&#46; Relevant reports have elucidated that variations in PD-1 and PD-L1 lead to aberrant PD-1&#47;PD-L repressive pathways&#44; resulting in aberrant immune function illnesses in the body&#46; Research has illuminated aberrant PD-L1 is involved in multiple tumors&#8217; immune escape mechanism and is nearly associated with tumors&#8217; occurrence and advancement&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> PCD-1 is also associated with increased proliferation of Treg cells and enhanced immunosuppressive function&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> Nevertheless&#44; few reports clearly elaborated on its association with immunotherapy&#39;s efficacy in LC patients&#46; Consequently&#44; this research was to explore the variations in PD-1 and PD-L1 in LC tissues and Peripheral Blood &#40;PPB&#41; and their association with immunotherapy&#39;s efficacy and prognosis&#44; offering reference for the clinical cure of the illness&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Materials and methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011"><span class="elsevierStyleItalic">Study design and clinical data</span></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Study design</span><p id="para0010" class="elsevierStylePara elsevierViewall">This trial was designed as a prospective&#44; parallel-group&#44; nonrandomized study and followed the criteria of the CONSORT statement&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">Clinical data</span><p id="para0011" class="elsevierStylePara elsevierViewall">From January 2014 to April 2018&#44; the involvement of 72 LC patients was as the LC&#44; and the inclusion of 39 patients with benign lung diseases in the identical period was as the benign&#46; Inclusion criteria&#58; 1&#41; Meet the diagnostic criteria for LC in the relevant guidelines&#59; 2&#41; Patients treated with PD-1&#47;PDL-1 antibodies&#59; 3&#41; Patients with complete clinical data&#46; Exclusion criteria&#58; 1&#41; Severe aberrant heart&#44; liver and kidney function&#59; 2&#41; Patients with immune diseases like combined systemic lupus erythematosus and rheumatoid&#59; 3&#41; Patients with severe complications during or after surgery&#59; 4&#41; Patients with severe metabolic illnesses like combined hypothyroidism&#59; 5&#41; Patients who underwent immunotherapy prior to enrollment&#59; 6&#41; Patients with PD-1&#47;PDL-1 antibodies to cure contraindications&#59; 7&#41; Patients with aberrant chest X-Ray or electrocardiogram&#46;</p><p id="para0012" class="elsevierStylePara elsevierViewall">This research was approved by Shanxi Provincial People&#39;s Hospital &#40;Approval number&#58; 201311S51&#41; Institutional Review Committee and Ethics Committee&#46; All participants received and signed informed consent&#46;</p></span></span></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014"><span class="elsevierStyleItalic">Methods</span></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">PD-1&#47;PDL-1&#8242;s detection in lung tissue</span><p id="para0013" class="elsevierStylePara elsevierViewall">Taking of postoperative tumor tissue&#39;s paraffin specimen with 3 &#956;m slice&#44; and baking was in the oven&#59; Dewaxing was with xylene&#44; complete submergence of the slices was in ethylene diamine tetraacetic acid alkaline repair solution&#44; and recovery of the antigen was implemented&#59; Dropwise addition of non-immune goat blocking antigen was to sections&#44; and introduction was conducted&#59; Dropwise addition of sections was with 1 antibodies &#40;rabbit anti-human PD-L1 monoclonal antibodies &#91;Abcam Technology Co&#46;&#44; Ltd&#46;&#44; ab213524&#93; and mouse anti-human PD-1 monoclonal antibodies &#91;Beijing Zhongshan Jinqiao Biotechnology Co&#46;&#44; Ltd&#46;&#44; Beijing&#44; China&#44; UMAB199&#93;&#41;&#59; After incubating&#44; addition of each section was into the secondary antibodies &#40;Immunoglobulin G antibodies-hypothalamic radial glial polymer&#41;&#59; Color development was with Diaminobenzidine solution&#44; and determination of color development was with distilled water&#44; Counterstaining was with hematoxylin counterstain&#44; dehydration was with conventional alcohol gradient&#44; fixation was with xylene&#44; and baking was in oven&#46; Adoption of neutral gum mount with known positive was as a control&#44; and exertion of polybutylacrylate instead of the primary antibodies was a negative control&#46; The location of PD-1 was in the cytoplasm with brown-yellow to tan particles appearing as positive color&#59; PD-L1&#8217;s location was in tumor cells and interstitial immune cell membrane&#47;intima system with brown-yellow to tan particles appearing as positive color&#46; <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a> for details&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">Examination of PD-1&#47;PDL-1 in PPB</span><p id="para0014" class="elsevierStylePara elsevierViewall">Collection of 5 mL fasting venous blood was from the patients&#59; After anticoagulation treatment&#44; the addition of d-Hanks solution with twice the volume and placing of Ficoll lymphocyte separation solution were implemented&#46; White blood cells&#8217; separation was conducted&#44; extraction of total RNA was via RNA extraction kit&#44; and test of RNA purity was via spectrophotometry &#40;OD<span class="elsevierStyleInf">260</span>&#47;OD<span class="elsevierStyleInf">280</span> &#8805; 1&#46;8 represented superior purity&#41;&#46; After taking 10 &#956;L amplified product&#44; performance of plate electrophoresis was on 2 &#37; agarose gel covering ethidium bromide&#46; After setting up the negative control&#44; reverse transcription of the negative control was not implemented&#44; observation of the positive was under an ultraviolet projection instrument&#44; and the red-orange fluorescence band at the identical level as the positive control was identified as positive&#46;</p></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">Immunotherapy</span><p id="para0015" class="elsevierStylePara elsevierViewall">All patients&#8217; cures were with PD-1&#47;PDL-1 antibodies &#40;Pembroliaumab&#44; Merck&#44; USA&#41; at a dose of 2 mg&#47;kg in a three-week course with intravenous infusion&#46; Curative efficacy assessment was in the light of Response Evaluation Criteria in Solid Tumors 1&#46;1&#44; and the patients&#8217; division was into complete remission&#44; partial remission&#44; and stable disease progression&#46; The patients&#8217; division was into the remission &#40;complete remission and partial remission&#41; and the non-remission &#40;stable disease and progression&#41; on the grounds of efficacy&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">Observation indexes</span><p id="para0016" class="elsevierStylePara elsevierViewall">&#40;1&#41; PD-1&#47;PDL-1&#8242;s comparison in lung tissue and PPB in the LC and the benign was to analyze the combined detection&#39;s diagnostic value for LC&#46; &#40;2&#41; PD-1&#47;PDL-1&#8242;s comparison in LC tissues and PPB in the remission and the non-remission was to analyze the association of PD-1&#47;PDL-1 with immunotherapy&#39;s efficacy&#46; &#40;3&#41; Patients&#8217; division was into the death and the survival in the light of 3-year survival after therapy&#46; Two-group comparison of PD-1&#47;PDL-1 in cancer tissues and PPB was to analyze predictive value with survival rate&#39;s relevance for patients&#8217; prognostic&#46;</p></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">Statistical processing</span><p id="para0017" class="elsevierStylePara elsevierViewall">Data processing was via applying SPSS22&#46;0 software&#46; Manifestation of enumeration data was in &#37;&#44; and comparison of the difference between groups was via exerting &#967;<span class="elsevierStyleSup">2</span> test&#46; Through normal test&#44; the representation of measurement data was in &#40;means &#177; standard deviation&#41;&#44; and the comparison of the difference between groups was via adopting <span class="elsevierStyleItalic">t</span>-test&#46; Analysis of PD-1&#47;PDL-1&#8242;s diagnostic value in lung tissue and PPB for LC was via adopting the Receiver Operating Characteristic &#40;ROC&#41; curve&#46; The survival curve&#39;s rendering was with GraphPad Prism 5 software&#44; and the test of the involved survival rate between the two was via adopting log-rank &#967;<span class="elsevierStyleSup">2</span>&#59; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;05 was accepted as indicative of dramatical differences&#46;</p></span></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020">Results</span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0021"><span class="elsevierStyleItalic">PD-1&#47;PDL-1&#8242;s comparison in lung tissue and PPB in the LC and the benign</span></span><p id="para0018" class="elsevierStylePara elsevierViewall">PD-1 and PDL-1&#8242;s positive rate in lung tissue and PPB in the LC was elevated vs&#46; the benign &#40;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#41;&#44; as presented in <a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0022"><span class="elsevierStyleItalic">Analysis of PD-1&#47;PDL-1&#8242;s diagnostic value in lung tissue and PPB for LC</span></span><p id="para0019" class="elsevierStylePara elsevierViewall">Area Under the Curve &#40;AUC&#41; of PD-1 and PDL-1 in lung tissue and PPB of LC of combined diagnosis was elevated vs&#46; each index&#39;s alone examination &#40;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#41;&#44; as manifested in <a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="tbl0003"></elsevierMultimedia><elsevierMultimedia ident="fig0001"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0023"><span class="elsevierStyleItalic">PD-1&#47;PDL-1&#8242;s comparison in cancer tissues and PPB of the remission with the non-remission</span></span><p id="para0020" class="elsevierStylePara elsevierViewall">PD-1 and PDL-1&#8242;s positive rate in cancer tissues and PPB in remission was declined vs&#46; the non-remission &#40;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#41;&#44; as presented in <a class="elsevierStyleCrossRef" href="#tbl0004">Table 4</a>&#46;</p><elsevierMultimedia ident="tbl0004"></elsevierMultimedia></span><span id="sec0016" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0024"><span class="elsevierStyleItalic">Analysis of PD-1&#47;PDL-1&#8242;s predictive value in cancer tissue and PPB on immunotherapy&#39;s efficacy</span></span><p id="para0021" class="elsevierStylePara elsevierViewall">AUC of the joint test in assessing immunotherapy&#39;s efficacy was augmented vs&#46; each index&#39;s alone examination &#40;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#41;&#44; as presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 5</a> and <a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0002"></elsevierMultimedia></span><span id="sec0017" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0025"><span class="elsevierStyleItalic">PD-1&#47;PDL-1 in cancer tissues and PPB in the death and the survival</span></span><p id="para0022" class="elsevierStylePara elsevierViewall">PD-1 and PDL-1&#8242;s positive rate in cancer tissues and PPB in the death was elevated vs&#46; the survival &#40;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#41;&#44; as manifested in <a class="elsevierStyleCrossRef" href="#tbl0006">Table 6</a>&#46;</p><elsevierMultimedia ident="tbl0006"></elsevierMultimedia></span><span id="sec0018" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0026"><span class="elsevierStyleItalic">Analysis of PD-1&#47;PDL-1&#8242;s predictive value in cancer tissue and PPB for patients&#8217; prognosis</span></span><p id="para0023" class="elsevierStylePara elsevierViewall">AUC of joint examination in predicting LC patients&#8217; prognosis was elevated vs&#46; each index&#39;s alone detection &#40;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#41;&#44; as manifested in <a class="elsevierStyleCrossRef" href="#tbl0007">Table 7</a> and <a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>&#46;</p><elsevierMultimedia ident="tbl0007"></elsevierMultimedia><elsevierMultimedia ident="fig0003"></elsevierMultimedia></span><span id="sec0019" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0027"><span class="elsevierStyleItalic">Comparison of patients&#8217; 3-year survival rate with PD-1&#47;PDL-1 in diverse cancer tissues</span></span><p id="para0024" class="elsevierStylePara elsevierViewall">Patients&#8217; 3-year survival rate with PD-1 positive was 45&#46;45 &#37; &#40;25&#47;55&#41;&#44; which was declined vs&#46; the negative patients 82&#46;35 &#37; &#40;14&#47;17&#41; &#40;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#41;&#46; PDL-1&#8242;s 3-year survival rates in cancer tissue in the positive and negative were 48&#46;78 &#37; &#40;20&#47;41&#41; and 61&#46;29 &#37; &#40;19&#47;31&#41;&#44; separately&#44; and no distinct differences were presented between the two &#40;<span class="elsevierStyleItalic">p</span> &#62; 0&#46;05&#41;&#44; as manifested in <a class="elsevierStyleCrossRef" href="#fig0004">Fig&#46; 4</a>&#46;</p><elsevierMultimedia ident="fig0004"></elsevierMultimedia></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0028">Discussion</span><p id="para0025" class="elsevierStylePara elsevierViewall">LC is tumor-linked death&#39;s primary reason all over the world&#46; Patients&#8217; asymptomatic period lasts for a long time owing to its insidious onset and easy confusion with benign pulmonary illnesses&#59; Multiple patients have been diagnosed with distant metastasis&#44; losing surgical cure opportunities&#44; and thus influencing their prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> Relevant reports have elaborated that LC&#39;s occurrence and advancement are linked with T cell immune deficiency in the body&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> PD-1&#47;PDL-1&#44; a co-stimulus analysis with negative regulatory function in the B7 family&#44; implicates in tumor immune escape mechanism via negative signal&#39;s limitation&#44; T-cell response&#39;s termination and attenuation&#44; thereby boosting tumor cell growth&#46;<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> Interrelated reports have illuminated PD-1&#47;PDL-1 in LC tissues is distinctly elevated&#46;<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> In this study&#44; PD-1 and PDL-1&#8242;s positive rates in lung tissue and PPB in the LC were augmented vs&#46; the benign&#44; clarifying that PD-1 and PDL-1&#8242;s positive rates in lung tissue and PPB in LC patients were elevated&#44; which was basically associated with the fact that PD-1&#47;PDL-1 was available to implicate in LC patients&#8217; immune modulation and the interaction between the two was available to mediate immune escape control in the engine body&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> This research&#39;s results elucidated AUC of PD-1 and PDL-1 in lung tissue and PPB of LC&#39;s joint diagnosis was elevated vs&#46; alone examination of each index&#44; clarifying that combined test was provided with diagnostic value for LC&#46;</p><p id="para0026" class="elsevierStylePara elsevierViewall">Presently&#44; LC&#39;s therapy strategies primarily cover radiotherapy&#44; chemotherapy&#44; targeted therapy and immunotherapy&#44; etc&#46; Meanwhile&#44; as tumor immunology advances&#44; immunotherapy has been paid extensive attention in diversified tumor illnesses&#46;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a> Immunotherapy for lung cancer is a therapeutic method to help the immune system recognize and clear cancer cells&#46;<a class="elsevierStyleCrossRef" href="#bib0017"><span class="elsevierStyleSup">17</span></a> Associated reports have illuminated the balance of tumor cells with the immune system exerts crucial action in tumors&#8217; occurrence and progression&#46;<a class="elsevierStyleCrossRef" href="#bib0018"><span class="elsevierStyleSup">18</span></a> The nature of the interaction between tumor cells and immune cells in the tumor microenvironment determines the antitumor response&#46; Recent studies have shown that immune cells play a dichotomous role in the evolution of lung tumors&#44; which can not only promote anti-tumor responses but also regulate the tumor microenvironment of immunosuppression &#40;pro tumorigenesis&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> Immune escape&#44; the prerequisite for tumor cells&#8217; generation&#44; overcomes the immune state&#44; activates the patient&#39;s own immune system and strengthens cellular immunity and humoral immune response in the engine body via introducing tumor antigens into patients in multiple forms&#44; thus exerting controlling and eliminating tumor cells&#8217; actions&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> Nevertheless&#44; numerous researches have elucidated that immunotherapy&#39;s effect varies greatly among diverse patients&#44; and several reports have manifested that immunotherapy&#39;s effect is linked with PD-1 in cancer tissues&#46;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> The PCD-1&#47;PD-Ls pathway plays a fundamental role in manipulating the magnitude of T-cell responses&#44; regulating their activation&#44; and generating immune tolerance in the Tumor Microenvironment &#40;TME&#41; and peripheral tissues&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> Previous studies showed that anti-PD-L1 antibody treatment effectively inhibited the growth of pancreatic tumors by activating cytotoxic T-cells&#44; and its anti-tumor immune mechanism mainly depended on the PD-L1 pathway and CD8 &#43; T<span class="elsevierStyleItalic">-</span>cells&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> Consequently&#44; relevant research in this study clarified PD-1 and PDL-1&#8242;s positive rates in cancer tissues and PPB in remission were declined vs&#46; the non-remission&#44; elaborating that immunotherapy&#8217; efficacy was associated with it&#44; which might be linked with the enhancement of tumor cells&#8217; immune escape via PD-1 and PDL-1&#8242;s positive&#46;</p><p id="para0027" class="elsevierStylePara elsevierViewall">Additionally&#44; the results of this research elaborated AUC of the joint test in assessing immunotherapy&#39;s efficacy was elevated vs&#46; each index&#39;s alone examination&#44; clarifying that the combined test was provided with appraisal value for immunotherapy&#39;s efficacy&#46;</p><p id="para0028" class="elsevierStylePara elsevierViewall">LC&#39;s good prognosis primarily relies on early diagnosis and cure&#44; while immunotherapy&#39;s application is available to distinctively prolong patients&#8217; survival and enhance patients&#8217; quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> Additionally&#44; this research&#39;s above results illuminated that PD-1 and PDL-1 were nearly associated with immunotherapy&#39;s efficacy&#44; elaborating that PD-1 and PDL-1 in patients might be associated with prognosis&#46; The results elucidated PD-1 and PDL-1&#8242;s positive rates in cancer tissues and PPB in the death were elevated vs&#46; the survival&#44; clarifying that patients with PD-1 and PDL-1&#8242;s positive in cancer tissues and PPB were provided with unpleasing prognosis&#46; The reason is that PD-1 is an inhibitory costimulatory molecule and PDL-1 is a stromal cell in tumor cells and microenvironment&#46; The combination of the two is available to restrain T-cells&#8217; function to lead to immune escape&#39;s occurrence&#44; thereby accelerating tumor cell growth&#46;<a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a> Additionally&#44; this study elaborated that patients&#8217; 3-year survival rate with positive PD-1 in cancer tissues declined vs&#46; the negative patients&#44; which further testified PD-1 in cancer tissues was linked with patients&#8217; prognosis&#46; Relevant research has illuminated PD-1 in LC tissues is available to influence T-cell activation to decline cytotoxic T-cells&#8217; tumor-killing efficacy&#44; thus influencing patients&#8217; prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a> Moreover&#44; PD-L1 expression in tumors or infiltrating immune cells has been demonstrated in a variety of tumors by immunohistochemistry&#44; indicating the role of the PD-1&#47;PD-L1 axis as a prognostic feature and therapeutic target in multiple tissue types&#46; Combining previous studies with these results&#44; PD-L1 can serve as a predictive biomarker for the response to PD-1&#47;PD-L1 inhibitors&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> While this study&#39;s results elaborated PD-1 was not associated with prognosis in cancer tissues in LC patients&#44; which was not assisted with the above research results&#44; which might be linked with this research&#39;s few sample sizes&#46; Consequently&#44; the sample size should be elevated later to analyze PD-1 and prognosis in the cancer tissues in LC patients&#46; Furthermore&#44; it is of high clinical value to further explore the quality of life of LC patients after immunotherapy&#46;</p><p id="para0029" class="elsevierStylePara elsevierViewall">In brief&#44; aberrant PD-1 with PDL-1 in cancer tissues and PPB was presented in LC patients&#44; and PD-1 with PDL-1&#8242;s combined test in cancer tissues and PPB was provided with diagnostic value for LC and assessment value for immunotherapy&#39;s efficacy with prognosis&#46;</p></span><span id="sec0021" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0029">Availability of data and materials</span><p id="para0030" class="elsevierStylePara elsevierViewall">The datasets used and&#47;or analyzed during the present study are available from the corresponding author on reasonable request&#46;</p></span><span id="sec0022" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0030">Ethical approval</span><p id="para0031" class="elsevierStylePara elsevierViewall">All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and&#47;or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards&#46; All subjects were approved by Shanxi Provincial People&#39;s Hospital &#40;Approval n&#186; 201311S51&#41;&#46;</p></span><span id="sec0023" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0031">Authors&#8217; contributions</span><p id="para0032" class="elsevierStylePara elsevierViewall">Jun Ma designed the research study&#46; JianRui Song and Lina Han performed the research&#46; Wen Zhou&#44; LiFeng Meng and JianHui Li provided help and advice&#46; JianRui Song&#44; Wen Zhou and XiaoMing Bai analyzed the data&#46; Jun Ma wrote the manuscript&#46; Jun Ma reviewed and edited the manuscript&#46; All authors contributed to editorial changes in the manuscript&#46; All authors read and approved the final manuscript&#46;</p></span><span id="sec0024" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0032">Funding</span><p id="para0033" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleGrantSponsor" id="gs0001">Shanxi Provincial Basic Research Program &#40;Free Exploration&#41;&#58; Natural Science Research</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0001">202103021224383</span>&#41;&#46;</p></span></span>"
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    "fechaRecibido" => "2023-10-26"
    "fechaAceptado" => "2024-05-16"
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            2 => "LC"
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      "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara015" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">&#8226;</span><p id="para0001" class="elsevierStylePara elsevierViewall">PD-1&#47;PDL-1&#8242;s comparison in cancer tissues and PPB of the remission with the non-remission&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">&#8226;</span><p id="para0002" class="elsevierStylePara elsevierViewall">Analysis of PD-1&#47;PDL-1&#8242;s predictive value in cancer tissue and PPB on immunotherapy&#39;s efficacy&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">&#8226;</span><p id="para0003" class="elsevierStylePara elsevierViewall">Comparison of patients&#8217; 3-year survival rate with PD-1&#47;PDL-1 in diverse cancer tissues&#46;</p></li></ul></p></span>"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Introduction</span><p id="spara016" class="elsevierStyleSimplePara elsevierViewall">This study aims to explore Programmed Death Receptor-1 &#40;PD-1&#41; and Programmed Death Ligand-1 &#40;PD-L1&#41; variations in Lung Cancer &#40;LC&#41; tissues and Peripheral Blood &#40;PPB&#41; and their association with immunotherapy efficacy and prognosis&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Method</span><p id="spara017" class="elsevierStyleSimplePara elsevierViewall">72 patients with LC were included in the LC group and 39 patients with concurrent benign lung disease were included in the benign group&#46; PD-1&#47;PDL-1 was compared in PPB and lung tissue&#46; All LC patients were treated with immunotherapy&#46; The relationship between PD-1&#47;PDL-1 in LC tissue and PPB and immunotherapy efficacy was analyzed&#46; Patients were divided into death and survival groups&#44; and PD-1&#47;PDL-1 in tumor tissues and PPB were compared&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Results</span><p id="spara018" class="elsevierStyleSimplePara elsevierViewall">The authors found that PD-1 and PDL-1 positive expression in lung tissue and PPB in LC patients was elevated&#46; Combined detection of PD-1 and PDL-1 was effective in diagnosing LC and evaluating the prognosis of LC patients&#46; PD-1 and PDL-1 positive expression was reduced after disease remission while elevated in dead patients&#46; The 3-year survival rate of patients with PD-1 positive expression was 45&#46;45 &#37; &#40;25&#47;55&#41;&#44; which was lower &#40;82&#46;35 &#37;&#44; 14&#47;17&#41; than those with PD-1 negative expression&#46; The 3-year survival rate of patients with positive and negative expression of PDL-1 was 48&#46;78 &#37; &#40;20&#47;41&#41; and 61&#46;29 &#37; &#40;19&#47;31&#41;&#44; respectively&#46;</p></span> <span id="abss0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0006">Discussion</span><p id="spara019" class="elsevierStyleSimplePara elsevierViewall">The present results demonstrated that PD-1 and PDL-1 are abnormal in cancer tissue and PPB of LC patients&#46; The combined detection of PD-1 and PDL-1 has diagnostic value for LC and evaluation value for the efficacy and prognosis of immunotherapy&#46;</p></span>"
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            "identificador" => "abss0004"
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        "identificador" => "fig0001"
        "etiqueta" => "Fig&#46; 1"
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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">PD-1&#47;PDL-1&#8242;S ROC curve analysis in lung tissue and PPB in LC&#39;s diagnosis&#46;</p>"
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        "etiqueta" => "Fig&#46; 2"
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          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">PD-1&#47;PDL-1&#8242;S ROC curve analysis in cancer tissues and PPB to predict immunotherapy&#39;s efficacy&#46;</p>"
        ]
      ]
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        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0003"
            "detalle" => "Fig&#46; 3&#58"
            "rol" => "short"
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        "descripcion" => array:1 [
          "en" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">PD-1&#47;PDL-1&#8242;S ROC curve analysis in cancer tissues and PPB to predict patients&#8217; prognostic&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "fig0004"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 953
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        "detalles" => array:1 [
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            "identificador" => "alt0004"
            "detalle" => "Fig&#46; 4&#58"
            "rol" => "short"
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        "descripcion" => array:1 [
          "en" => "<p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Comparison of patients&#8217; 3-year survival rates with PD-1&#47;PDL-1 in diverse cancer tissues&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0001"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
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                  <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" style="border-bottom: 2px solid black">Classification&nbsp;\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" style="border-bottom: 2px solid black">The LC &#40;<span class="elsevierStyleItalic">n</span> &#61; 72&#41;&nbsp;\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="" valign="top" scope="col" style="border-bottom: 2px solid black">The benign &#40;<span class="elsevierStyleItalic">n</span> &#61; 39&#41;&nbsp;\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" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">&#967;<span class="elsevierStyleSup">2</span>&#47;t</span>&nbsp;\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" style="border-bottom: 2px solid black">p&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="en0006"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Gender &#40;cases&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0007"></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="en0008"></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="en0009"></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="en0010"></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="en0011"></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="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">51&nbsp;\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">23&nbsp;\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">1&#46;601&nbsp;\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">0&#46;206&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0016"></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="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21&nbsp;\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">16&nbsp;\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">&nbsp;\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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Age &#40;years&#41;&nbsp;\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">58&#46;95 &#177; 6&#46;24&nbsp;\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">57&#46;73 &#177; 6&#46;75&nbsp;\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">0&#46;955&nbsp;\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">0&#46;341&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Course of disease &#40;months&#41;&nbsp;\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">15&#46;29 &#177; 2&#46;12&nbsp;\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">14&#46;85 &#177; 2&#46;36&nbsp;\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">1&#46;003&nbsp;\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">0&#46;318&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\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">21&#46;09 &#177; 1&#46;87&nbsp;\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">21&#46;67 &#177; 1&#46;75&nbsp;\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">1&#46;595&nbsp;\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">0&#46;114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Smoking history &#40;cases&#41;&nbsp;\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">31&nbsp;\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">13&nbsp;\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">0&#46;999&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">0&#46;317&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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Pulmonary diseases&#8217; history &#40;cases&#41;&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">62&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">29&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">2&#46;365&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">0&#46;124&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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Tumor&#39;s family history &#40;cases&#41;&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">9&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">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;606&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;436&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Lesion site &#40;cases&#41;&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">&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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></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="en0055"></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="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Left&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">29&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">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;735&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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Right&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">43&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">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></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="en0065"></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="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Educational background &#40;cases&#41;&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">&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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0069"></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="en0070"></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="en0071"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">High school and above&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">42&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">21&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">0&#46;208&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">0&#46;649&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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Junior high school and below&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">30&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">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0079"></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="en0080"></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="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Monthly income &#40;cases&#41;&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">&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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></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="en0085"></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="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5000 yuan or more&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">39&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">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;629&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;202&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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Less than 5000 yuan&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">33&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">13&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></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3692172.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara005" class="elsevierStyleSimplePara elsevierViewall">Comparison of general data between the two&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0002"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0006"
            "detalle" => "Table 2&#58"
            "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="en0096"></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">Groups&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0097"></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">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0098"></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">Cancer tissue PD-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0099"></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">Cancer tissue PDL-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0100"></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">PPB PD-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0101"></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">PPB PDL-1&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="en0102"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">The LC&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">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">55 &#40;76&#46;39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">41 &#40;56&#46;94&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0106"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">34 &#40;47&#46;22&#41;&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">24 &#40;33&#46;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0108"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">The benign&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0109"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8 &#40;20&#46;51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0111"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6 &#40;15&#46;38&#41;&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">41 &#40;0&#46;26&#41;&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">4 &#40;10&#46;26&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0114"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleItalic">&#967;<span class="elsevierStyleSup">2</span></span>&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><a name="en0116"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">32&#46;180&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">17&#46;897&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">15&#46;354&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0119"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7&#46;142&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0120"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0121"></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="en0122"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60; 0&#46;001&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">&#60; 0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60; 0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3692176.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara006" class="elsevierStyleSimplePara elsevierViewall">Comparison of PD-1&#47;PDL-1 in lung tissue and PPB of the LC and the benign &#40;cases&#44;&#37;&#41;&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0003"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0007"
            "detalle" => "Table 3&#58"
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spara008" class="elsevierStyleSimplePara elsevierViewall">Vs&#46; the combination&#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">Index&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">AUC&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">SE&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="" valign="top" scope="col" style="border-bottom: 2px solid black">95 &#37; CI&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">Lung tissue PD-1&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">0&#46;779&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">0&#46;047&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="" valign="top">0&#46;686&#8764;0&#46;872&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">Lung tissue PDL-1&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">0&#46;708<a class="elsevierStyleCrossRef" href="#tb3fn1"><span class="elsevierStyleSup">a</span></a>&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">0&#46;050&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="" valign="top">0&#46;609&#8764;0&#46;806&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">PPB PD-1&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">0&#46;685<a class="elsevierStyleCrossRef" href="#tb3fn1"><span class="elsevierStyleSup">a</span></a>&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">0&#46;051&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="" valign="top">0&#46;586&#8764;0&#46;784&nbsp;\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">PPB PDL-1&nbsp;\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">0&#46;615<a class="elsevierStyleCrossRef" href="#tb3fn1"><span class="elsevierStyleSup">a</span></a>&nbsp;\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">0&#46;054&nbsp;\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="" valign="top">0&#46;510&#8764;0&#46;721&nbsp;\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">Combination&nbsp;\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">0&#46;841&nbsp;\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">0&#46;039&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;765&#8764;0&#46;917&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                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="en0150"></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">Groups&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0151"></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">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0152"></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">Cancer tissue PD-1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Cancer tissue PDL-1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">PPB PD-1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">PPB PDL-1&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="en0156"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">The non-remission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0157"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0158"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26 &#40;96&#46;30&#41;&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">24 &#40;88&#46;89&#41;&nbsp;\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">19 &#40;70&#46;37&#41;&nbsp;\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="" valign="top">13 &#40;48&#46;15&#41;&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
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">The remission&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">45&nbsp;\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">29 &#40;64&#46;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0165"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17 &#40;37&#46;78&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0166"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;33&#46;33&#41;&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">11 &#40;24&#46;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0168"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleItalic">&#967;<span class="elsevierStyleSup">2</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0169"></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="en0170"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">9&#46;492&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">17&#46;980&nbsp;\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">9&#46;288&nbsp;\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="" valign="top">4&#46;267&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">P&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">&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">0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0177"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60; 0&#46;001&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">0&#46;002&nbsp;\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">0&#46;039&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  <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="en0180"></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">Index&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">AUC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">SE&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">95 &#37; CI&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="en0184"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cancer tissue PD-1&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">0&#46;659<a class="elsevierStyleCrossRef" href="#tb5fn1"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0186"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;063&nbsp;\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">0&#46;535&#8764;0&#46;784&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0188"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cancer tissue PDL-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0189"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;756<a class="elsevierStyleCrossRef" href="#tb5fn1"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0190"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;058&nbsp;\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">0&#46;642&#8764;0&#46;869&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0192"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">PPB PD-1&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">0&#46;685<a class="elsevierStyleCrossRef" href="#tb5fn1"><span class="elsevierStyleSup">a</span></a>&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">0&#46;065&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0195"></a><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0196"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">PPB PDL-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0197"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;619<a class="elsevierStyleCrossRef" href="#tb5fn1"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0198"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">0&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0199"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">0&#46;482&#8764;0&#46;756&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0200"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">Combination&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" scope="col" style="border-bottom: 2px solid black">Cancer tissue PD-1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t  " align="" valign="top">7 &#40;17&#46;95&#41;&nbsp;\t\t\t\t\t\t\n
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                            0 => "Y&#46; Cho"
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                            3 => "C&#46;G&#46; Lee"
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