The two major histological types of gastric cancer, intestinal and diffuse subtypes, have distinct epidemiological and pathophysiological features and were also suggested to be of diverse clinical outcomes. Although the gene expression spectrum of gastric cancer subtypes has been reported by previous studies, its linkage with gastric cancer clinical features and outcomes remains elusive. We investigated large-sample online gastric cancer datasets for seeking genes correlated with the clinical diversities between gastric cancer intestinal and diffuse subtypes. Genes differently expressed between the two subtypes were assessed by multiple statistical analysis and were testified on cellular level by quantitative RT-PCR. Related genes were combined to generate a risk signature, and their mutual linkages were also explored. Among genes overexpressed in intestinal subtype, ATPIF1, PRDX2, PRKAR2A, and SMC1A were correlated with positive prognosis. Among genes overexpressed in diffuse subtype, DTNA, GPR161, IDS, RHOQ, and TSHZ2 were correlated with negative prognosis. These nine genes were all novel independent prognostic factors. When used in combination as signatures, these two gene sets displayed strong efficacy for prediction of the prognosis and clinical variables in gastric and colorectal cancer. Hence, these two genes sets were respectively defined as the favorable intestinal-like and adverse diffuse-like gene sets. We identified nine novel genes correlated with the clinical diversity between the intestinal and diffuse subtypes of gastric cancer. The malignant changes from the intestinal to diffuse subtype might be due to the reduction of the four intestinal-like genes, as well as the elevation of the five diffuse-like genes.
Keywords: Gastric cancer; Lauren classification; Prognostic markers; Risk signatures; Subtype-related genes.