A four-DNA methylation signature as a novel prognostic biomarker for survival of patients with gastric cancer

BACKGROUND: Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related mortality. Lack of prognostic indicators for patient survival hinders GC treatment and survival. METHODS AND RESULTS: Methylation profile data of patients with GC obtained from The Cancer Genome Atlas (TCGA) database were analyzed to identify methylation sites as biomarkers for GC prognosis. The cohort was divided into training and validation sets. Univariate Cox, LASSO regression,and multivariate Cox analyses revealed a close correlation of a four-DNA methylation signature as a risk score model with the overall survival of patients with GC. The survival between high-risk and low-risk score patients with GC was significantly different. Analyses of receiver operating characteristics revealed a high prognostic accuracy of the four-DNA methylation signature in patients with GC. The subgroup analysis indicated that the accuracy included that for anatomical region, histologic grade, TNM stage, pathological stage, and sex. The GC prognosis based on the four-DNA methylation signature was more precise than that based on known biomarkers. CONCLUSIONS: The four-DNA methylation signature could serve as a novel independent prognostic factor that could be an important tool to predict the prognostic outcome of GC patients. This potential must be verified in a large-scale population cohort study and through basic research studies.