Aim: To study fibrosis, angiogenesis, oxidative stress and inflammation markers in diabetic and non-diabetic patients with gastric cancer (GC).
Introduction: Type 2 Diabetes mellitus (DM2) is a major health problem, with 415 million people diagnosed worldwide.1 Evidence regarding its association with various types of cancer has been reported, including GC.2 Some hypotheses have been suggested to explain how DM2 could enhance the risk of cancer development, such as hyperglycemia, hyperinsulinemia, oxidative stress, vascular disturbances and a chronic low inflammation state.3–5
Gastric cancer (GC) is the fifth most common cancer worldwide and ranks as the third leading cause of cancer-related death.6 GC is frequently associated with infection by Helicobacter pylori and inflammation plays a central role in the carcinogenic process. Such chronic inflammatory state, linked with angiogenesis imbalance, oxidative stress and metabolic signaling, suggests that also DM2 might be a major risk factor in initiation and progression of GC, demanding further investigation.
Methods: A series of GC from DM2 (n=22) and nonDM2 (n=21) patients were studied. Immunohistochemistry (IHC) using antibodies against CD31 and 3-Nitrotyrosine was performed, to assess density of vessels and oxidative stress status. Histochemical staining with Sirius red was performed to determine the percentage of fibrosis in the tumor and non-neoplastic adjacent mucosa. Based on assessment of tumor inflammatory cell infiltrate and tumor stroma percentage, a semi-quantitative evaluation of Glasgow Microenvironment Score7 was performed. Also, Glasgow Prognostic Score, that is widely known as a systemic inflammatory-based marker, was determined for each patient.8
Results: Diabetic patients presented a significant higher glycaemia than the control patients (190.1±13.6mg/dL vs 98.2±3.6mg/dL, p<0.001, respectively). Decreased survival rates were observed in diabetic patients (611.5 vs 916.0, p=ns). Tumours exhibited increased fibrosis relatively to the adjacent mucosa in both groups and diabetic patients (N: 9.362±1.337; T: 12.29±1.407) presented higher fibrosis levels than the non-diabetic patients (N: 7.165±1.017; T: 10.97±1.076).
Conclusion: Expected results: Identifying the distinct features that characterize GC of DM2 patients compared to nondiabetic patients (namely fibrosis, angiogenesis, inflammation, and oxidative stress biomarkers) will enable to study this subset of GC patients and unravel key mechanisms behind the relationship between DM2 and GC.
Acknowledgements: Funding: This work was supported by the project Diabetes & obesity at the crossroads between Oncological and Cardiovascular diseases – a system analysis NETwork towards precision medicine (DOCnet) – A multi-omics approach to decipher diabetes-related molecular targets in cancer: a step towards precision medicine. NORTE2020 - “Programa Operacional Regional do Norte” (NORTE-01-0145-FEDER-000003) (Jan 2016-Dez2018).