An immune-related gene signature predicts prognosis of gastric cancer

Background: Although the outcome of patients with gastric cancer (GC) has improved significantly with the recent implementation of annual screening programs. Reliable prognostic biomarkers are still needed due to the disease heterogeneity. Increasing pieces of evidence revealed an association between immune signature and GC prognosis. Thus, we aim to build an immune-related signature that can estimate prognosis for GC. Methods: For identification of a prognostic immune-related gene signature (IRGS), gene expression profiles and clinical information of patients with GC were collected from 3 public cohorts, divided into training cohort (n=300) and 2 independent validation cohorts (n=277 and 433 respectively). Results: Within 1811 immune genes, a prognostic IRGS consisting of 16 unique genes was constructed which was significantly associated with survival (hazard ratio [HR], 3.9 [2.78-5.47]; P < 1.0 x 10(-22)). In the validation cohorts, the IRGS significantly stratified patients into high-vs low-risk groups in terms of prognosis across (HR, 1.84 [1.47-2.30]; P = 6.59 x 10(-8)) and within subpopulations with stage I&II disease (HR, 1.96 [1.34-2.89]; P = 4.73 x 10(-4)) and was prognostic in univariate and multivariate analyses. Several biological processes, including TGF-beta and EMT signaling pathways, were enriched in the high-risk group. T cells CD4 memory resting and Macrophage M2 were significantly higher in the high-risk risk group compared with the low-risk group. Conclusion: In short, we developed a prognostic IRGS for estimating prognosis in GC, including stage I&II disease, providing new insights into the identification of patients with GC with a high risk of mortality.