Microsatellite instability and Epstein-Barr virus combined with PD-L1 could serve as a potential strategy for predicting the prognosis and efficacy of postoperative chemotherapy in gastric cancer

作者：Na Yang, Yanhua Wu, Meishan Jin, Zhifang Jia, Yueqi Wang, Donghui Cao, Lili Qin, Xueying Wang, Min Zheng, Xueyuan Cao, Jing Jiang · 发表于：PeerJ · 年份：2021 · DOI：10.7717/peerj.11481 · 被引用次数：20 · 研究领域：Cancer Immunotherapy and Biomarkers、Gastric Cancer Management and Outcomes、Genetic factors in colorectal cancer

Background Microsatellite instability (MSI) and Epstein-Barr virus (EBV)-positive molecular subtypes exhibit complex immune responses in gastric cancer (GC), and PD-L1 has emerged as a prognostic biomarker associated with the cancer immune microenvironment. This study aimed to determine the prognostic value of molecular subtypes and whether the addition of PD-L1 would accurately predict the prognosis and guide postoperative chemotherapy for GC patients. Methods We performed molecular subtyping of tissue microarray slides from 226 GC patients who were treated with radical gastrectomy. The MSI status and PD-L1 expression were evaluated through immunohistochemistry (IHC) and EBV status through situ hybridization. Multiplex polymerase chain reaction (PCR) was also performed on 50 cases to validate the accuracy of IHC in defining MSI status. Differences in overall survival (OS) were assessed using the Kaplan-Meier method, log-rank test and Cox proportional hazards regression model. Results Among the 226 GC patients, 52 (23.2%) patients were classified as the MSI subtype, 11 (4.9%) were EBV + subtype, and 161 (71.9%) were MSS (Microsatellite stable) /EBV − subtype according to TCGA analysis. Two patients were both positive for MSI and EBV infection. EBV + cases showed higher PD-L1 positivity than MSI cases and MSS/EBV − cases (81.8% vs. 50.0% vs. 35.4%, P = 0.003). Compared with the non-MSS/EBV − (MSI or EBV + cases) subgroup, GC patients with MSS/EBV − were associated with the wor...