Clinicopathological features of tumor mutation burden, Epstein-Barr virus infection, microsatellite instability and PD-L1 status in Chinese patients with gastric cancer

Abstract Objectives Gastric cancer (GC) is the 4th most common type of worldwide. Different GC subtypes have unique molecular features that may different therapeutic methods. The aim present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, expression programmed death-ligand 1 (PD-L1) and gene mutations in patients. Methods data 2504 patients, who underwent curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 2018, were reviewed. We analyzed clinicopathological factors associated immunohistochemistry (IHC) profiles these genetic alterations using next generation sequencing (NGS). Results Mismatch repair-deficient (d-MMR) patients found a higher probability expressing PD-L1 ( p = 0.000, cutoff value 1%). In addition, 4 6.9% gastric EBV-positive d-MMR, respectively. number MLH1/PMS2-negative cases 126 (6%), MSH2/MSH6-negative 14 (0.9%). d-MMR status intestinal group 0.012), but not tumor differentiation. Furthermore, MSI (detected by NGS IHC, respectively) consistently high, rate GC. A genes DNA damage repair detected MSI, including POLE, ETV6, BRCA RNF43. high mutation burden, significantly mutated LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 PIK3CA NOTCH1 SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) ATM (39.53%). Conclusions Using IHC NGS, protein expression, burden (TMB) identified GC, which provides theoretical basis for future clinical treatment