Development and Experimental Validation of a Novel Prognostic Signature for Gastric Cancer

SIMPLE SUMMARY: Gastric cancer (GC) accounts for a considerable amount of morbidity and mortality worldwide. This study developed and experimentally validated a prognostic risk gene signature (PRGS). This is a stable and robust signature for assessing the prognosis of gastric cancer. We performed multiple analyses through consensus clustering and binary classification to assess the robustness of the PRGS in other independent datasets. Additionally, this PRGS exhibited a superior accuracy compared to most traditional clinical markers, including molecular features, and other published signatures. Besides, we also detected the tumor purity, immune cell infiltration, and oncogenic mutation status of high- and low-PRGS groups. ABSTRACT: Background: Gastric cancer is a malignant tumor with high morbidity and mortality. Therefore, the accurate recognition of prognostic molecular markers is the key to improving treatment efficacy and prognosis. Methods: In this study, we developed a stable and robust signature through a series of processes using machine-learning approaches. This PRGS was further experimentally validated in clinical samples and a gastric cancer cell line. Results: The PRGS is an independent risk factor for overall survival that performs reliably and has a robust utility. Notably, PRGS proteins promote cancer cell proliferation by regulating the cell cycle. Besides, the high-risk group displayed a lower tumor purity, higher immune cell infiltration, and lower oncogenic mutation than the low-PRGS group. Conclusions: This PRGS could be a powerful and robust tool to improve clinical outcomes for individual gastric cancer patients.