Prognostic Value of Epstein-Barr Virus Infection in Patients with Gastric Cancer: A Meta-Analysis

Background: Since Epstein-Barr virus (EBV)-encoded small RNAs (EBER) has become the standard for detection of EBV, the prognostic role of EBV infection in gastric cancer (GC) remains controversial. The main aim of this meta-analysis was to determine the correlation between EBV infection and the prognosis of GC. Methods: : We systematically searched PubMed and EMBASE to identify eligible studies to review up to June 23,2021. Pooled hazard ratios with 95% confidence intervals were calculated using the fixed effects model or random-effects model for overall survival (OS). Sensitivity and subgroup analyses were also performed, and publication bias was assessed by using Stata 14.0. Results: : 35 studies comprising 26163 patients with GC were included in this meta-analysis. After pooling all studies, EBV-positive patients were noted to have better OS than EBV-negative patients (HR: 0.72, 95% CI: 0.59-0.84, P < 0.001), though with high heterogeneity (I 2 51.7%). In subgroup analysis, similar conclusion can be drawn for patients in Asian and American, while for patients in Europe EBV infection is not a prognostic indicator. Apart from that, studies conducted in Asia and Europe, statistical method of multivariate analysis, high quality score, all had significant heterogeneity. Pooled data based on sensitivity analyses did not change the conclusion. Conclusions: : EBV infection was associated with better OS in patients with GC. These results differed between studies due to differences in region, which need further study to clarify its prognostic significance. Prospero registration number: CRD42021262332.