Comprehensive molecular characterization and identification of prognostic signature in stomach adenocarcinoma on the basis of energy-metabolism-related genes.

ABSTRACT

BACKGROUND: Stomach adenocarcinoma (STAD) is a leading cause of cancer deaths, but its molecular and prognostic characteristics has never been fully illustrated. AIM: To describe a molecular evaluation of primary STAD and develop new therapies and identify promising prognostic signatures. METHODS: We describe a comprehensive molecular evaluation of primary STAD based on comprehensive analysis of energy-metabolism-related gene (EMRG) expression profiles. RESULTS: On the basis of 86 EMRGs that were significantly associated to patients' progression-free survival (PFS), we propose a molecular classification dividing gastric cancer into two subtypes Cluster 1, most of which are young patients and display more immune and stromal cell components in tumor microenvironment and lower tumor priority; and Cluster 2, which show early stages and better PFS. Moreover, we construct a 6-gene signature that can classify the prognostic risk of patients after a three-phase training test and validation process. Compared with patients with low-risk score, patients with high-risk score had shorter overall survival. Furthermore, calibration and DCA analysis plots indicate the excellent predictive performance of the 6-gene signature, and which present higher robustness and clinical usability compared with three previous reported prognostic gene signatures. According to gene set enrichment analysis, gene sets related to the high-risk group were participated in the ECM receptor interaction and hedgehog signaling pathway. CONCLUSION: Identification of the EMRG-based molecular subtypes and prognostic gene model provides a roadmap for patient stratification and trials of targeted therapies.