Bayesian hierarchical lasso Cox model: A 9-gene prognostic signature for overall survival in gastric cancer in an Asian population.

Abstract

ObjectiveGastric cancer (GC) is one of the most common tumour diseases worldwide and has poor survival, especially in the Asian population. Exploration based on biomarkers would be efficient for better diagnosis, prediction, and targeted therapy.MethodsExpression profiles were downloaded from the Gene Expression Omnibus (GEO) database. Survival-related genes were identified by gene set enrichment analysis (GSEA) and univariate Cox. Then, we applied a Bayesian hierarchical lasso Cox model for prognostic signature screening. Protein-protein interaction and Spearman analysis were performed. Kaplan–Meier and receiver operating characteristic (ROC) curve analysis were applied to evaluate the prediction performance. Multivariate Cox regression was used to identify prognostic factors, and a prognostic nomogram was constructed for clinical application.ResultsWith the Bayesian lasso Cox model, a 9-gene signature included TNFRSF11A, NMNAT1, EIF5A, NOTCH3, TOR2A, E2F8, PSMA5, TPMT, and KIF11 was established to predict overall survival in GC. Protein-protein interaction analysis indicated that E2F8 was likely related to KIF11. Kaplan-Meier analysis showed a significant difference between the high-risk and low-risk groups (P<0.001). Multivariate analysis demonstrated that the 9-gene signature was an independent predictor (HR = 2.609, 95% CI 2.017–3.370), and the C-index of the integrative model reached 0.75. Function enrichment analysis for different risk groups revealed the most significant enrichment pathway/term, including pyrimidine metabolism and respiratory electron transport chain.ConclusionOur findings suggested that a novel prognostic model based on a 9-gene signature was developed to predict GC patients in high-risk and improve prediction performance. We hope our model could provide a reference for risk classification and clinical decision-making.