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

PeerJ

article

Na Yang¹  Yanhua Wu¹  Meishan Jin²  Zhifang Jia¹  Yueqi Wang¹  Donghui Cao¹  Lili Qin¹  Xueying Wang¹  Min Zheng¹  Xueyuan Cao⁴  Jing Jiang¹ 

[1] Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin Province;Division of Pathology, First Hospital of Jilin University, Changchun, Jilin Province;Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin Province;Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin Province

关键词: Microsatellite instability;    Epstein-Barr virus;    PD-L1;    Gastric cancer;    Postoperative chemotherapy;    Overall survival;   

DOI  :  10.7717/peerj.11481

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundMicrosatellite 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.MethodsWe 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.ResultsAmong 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 worst outcomes (HR = 1.610, 95% CI [1.046–2.479], P = 0.031). MSS/EBV− GCs alone could benefit from postoperative chemotherapy (HR = 0.452, 95% CI [0.299–0.682], P < 0.001), and PD-L1-positive expression could also predict a better prognosis (HR = 0.612, 95% CI [0.389–0.962], P = 0.033) in this subgroup. Considering both chemotherapy efficacy and PD-L1 expression in the MSS/EBV− subgroup, chemotherapy could improve the prognosis for PD-L1-negative MSS/EBV− GCs (HR = 0.357, 95% CI [0.217–0.587], P < 0.001) but not PD-L1-positive MSS/EBV− GCs.ConclusionsMolecular subtyping combined with PD-L1 expression could serve as a potential strategy to better predict prognosis and guide postoperative chemotherapy of GC patients.

【 授权许可】

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