Methylation-based subtypes of gastric cancer provide distinct prognostic impact in patients who receive chemotherapy

High levels of cancer-specific aberrant promoter hypermethylation provide distinct clinicopathological features in gastric cancer (GC) patients. This study explored the molecular subtypes based on the cancer-specific aberrant promoter hypermethylation to predict prognosis of advanced stage GC treated by the chemotherapy. Using five methylated in tumors (MINT) loci (MINT1, 2, 12, 25, and 31), cancer-specific aberrant promoter hypermethylation was characterized in 186 advanced stage GCs receiving chemotherapy (stages II, III and IV diseases). We found that the both methylation-high (4 or 5 markers positive) and negative (one or 0 marker positive) cases presented significantly worse overall survival (OS) and progression free survival ( P  = 0.003, 0.009, respectively). Multivariate survival analysis using Cox's regression model demonstrated that cases with stage IV and methylation-negative were significantly associated with worse OS (stage IV, hazard ratio [HR] = 4.33, 95% confidence interval [CI] = 2.26–8.31, P  < 0.0001; methylation-negative, HR = 2.43, 95%CI = 1.29–4.59, P  = 0.006;), while cases in the middle third was also associated with better OS (HR = 0.48, 95%CI = 0.24–0.98, P  = 0.045;). Our result show that the cancer-specific epigenetic anomaly provides prognostic impact in patients with GC treated by chemotherapy.