Clinic-pathological Features of Epstein-barr Virus Infection, Microsatellite Instability, Tumor Mutation Burden and PD-L1 Status in 2504 Chinese Gastric Cancer Patients

Abstract

Objectives: Gastric cancer is the 4th most common cancer worldwide. Different subtype showed unique molecular features that could potentially guide therapeutic decisions. The aim of this study was to investigate the Epstein-Barr virus infection, microsatellite instability status, PD-L1 expression and gene mutation in surgically treated gastric cancer patients. Methods: We reviewed all GC patients who underwent potentially curative gastroectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018 from a prospective collected medical database. We analyzed the clinic-pathological factors associated with immunohistochemistry profiles. We also analyzed gene changes through next-generation sequencing. Results: d-MMR gastric cancer patients are more likely to expression programmed death-ligand 1 (p<0.001, programmed death-ligand 1 cut off value 1%). EBV-positive and d-MMR patients were identified in 4% and 7.5% of the 2504 gastric cancer patients, respectively. The MLH1/PMS2 negative case number was 126. The MSH2/MSH6 negative case number was 14. d-MMR status was related to diffuse/mixed group (p<0.05), but not related to tumor differentiation. In our study, the microsatellite instability results detected by next generation sequencing and d-MMR gastric cancer results detected by immunohistochemistry were in high consistency. d-MMR gastric cancer patients had more microsatellite instability core. Many pathogenic genes were detected in microsatellite instability gastric cancer patients, such as POLE, ETV6, TP53, BRCA, RNF43 and other genes. Conclusion: Through immunohistochemistry and next generation sequencing, we got MSI status, protein expression, TMB and gene changes of GC, which provided a theoretical basis for future G clinical treatment.