Expression Pattern and Prognostic Value of p53-Pathway in Gastric Cancer

Background: Gastric cancer is one of the most common cancer across the world. Increasing evidence suggest that p53-pathway plays a critical role in the initiation, progress and therapy of gastric cancer. However, the prognostic value of p53-pathway in gastric cancer is not fully understood. Methods: A total of 67 p53-pathway-related genes and corresponding clinical information of 415 gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. The consensus clustering algorithm were performed to analyze the expression level of all p53-pathway related genes. Based on the differentially expressed genes between different subgroups, Cox regression analysis were used to construct an independent prognostic signature, which was further validated in two external datasets. Results: 3 subgroups of patients with significant different survival outcome were identified according to the expression level of p53-pathway-related genes. Comparison of gene expression between those subgroups identified 12 differentially expressed genes, 3 (THBS1, SERPINE1 and GADD45B) of which were significantly associated with the overall survival outcome. We further constructed a 3-gene signature as independence prognosis signature with promising performance in survival prediction of gastric cancer. Conclusions: This study provides a potential prognostic signature for predicting prognosis of gastric cancer patients, which may benefit individual therapy of gastric cancer.