In this study, we performed an integrative analysis to identify the epigenetic changes that may play key role in the initiation and progression of GC, based on which we developed a DNA methylation signature consisting of ten gene members (SCNN1B, NFE2L3, CLDN2, RBPMS2, JPH2, GBP6, COL4A5, SMKR1, PPP1R14A, and ARL4D) to improve survival prediction of GC. The gene discussed is CLDN2; the disease is gastric cancer.