Prognosis of EBV-positive gastric cancer with lymphoid stroma: systematic review and meta-analysis

Background Although gastric cancer with lymphoid stroma (GCLS) presents better prognosis, uncertainty still exists regarding the association of Epstein-Barr virus (EBV) infection with prognosis of GCLS. Therefore, it is urgent to evaluate the outcome and characteristics of EBV-positive GCLS via a systematic review and meta-analysis.Methods Three medical databases, with a period ranging from 2000 to so far, were searched for observational studies on EBV infection, clinical characteristics and prognosis. Odds ratio (OR) was used to evaluate the mortality and clinical characteristics of EBV-positive GCLS patients. Egger's test and subgroup analysis were conducted to identify the source of heterogeneity.Results Nine retrospective studies were finally identified, which involved 618 EBV-positive and 153 EBV-negative GCLS patients. The forest plot indicated that EBV-positive GCLS patients had lower mortality (p = .009; 95% CI: 0.15-0.77; I-2 = 48.6%). Both of funnel plot and Egger's tests suggested that there was no publication bias. Nonetheless, subgroup analysis indicated that T1-2 stage ratio more than 50% (p < .001; I-2 = 6.7%) and male ratio more than 80% (p < .001; I-2 = 0.0%) were valuable for eliminating the heterogeneity. Seven studies including valid information showed that TNM stage of EBV-positive and negative GCLS patients was not statistically different (p = .644; 95% CI: 0.50-1.53; I-2 = 0.0%).Conclusions EBV-positive GCLS tends to have lower mortality, suggesting that detection of EBV infection is necessary to predict prognosis of GCLS.