Runt-related transcription factor 3 promoter hypermethylation and gastric cancer risk: A meta-analysis

Abstract Objective The aim of this study was to investigate the correlation between runt-related transcription factor 3 (RUNX3) gene promoter hypermethylation and gastric cancer risk by meta-analysis. Methods By searching Medline, PubMed, Embase, Cochrane, Ovid and CNKI electronic databases, the open published studies about the association between RUNX3 gene promoter hypermethylation and gastric cancer risk were screened. The hypermethylation rate in cancer tissue and autologous control tissue (normal gastric tissue of gastric cancer patients) were extracted from each included study. The odds ratio (OR) and corresponding 95% confidence interval (95% CI) of RUNX3 gene promoter hypermethylation in cancer tissue versus autologous control tissue of gastric cancer patients were pooled with random or fixed effect models. The publication bias was evaluated by Begg’s funnel plot and Egger’s line regression test. Results Finally, twenty three relevant studies were included in this meta-analysis. The hypermethylation rate in cancer tissue and autologous control tissue of gastric cancer patients were 0.56±0.16 and 0.18±0.22 respectively, which demonstrated a hypermethylation rate in cancer tissue significantly higher than that of autologous controls (P<0.05). A significant positive correlation of hypermethylation rate between cancer tissue and autologous control existed for the included 23 studies(r pearson =0.62, P<0.05). For significant heterogeneity across the studies, the OR was pooled by random effects model. The combined OR was 8.06 with the 95% CI of 5.73~11.32, which indicated the hypermethylation frequency in cancer tissue was higher than that of autologous controls. Conclusion The RUNX3 gene promoter hypermethylation rate was much higher in cancer tissue than that of normal gastric tissue in patients with gastric cancer, which indicates a close association between gastric cancer and RUNX3 gene promoter hypermethylation. Furthermore, RUNX3 gene promoter hypermethylation may be a potential biomarker for gastric cancer diagnosis.