A predictive model using four ferroptosis-related genes accurately predicts gastric cancer prognosis.

Gene expression profiles of people with GC and Helicobacter pylori-associated GC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The FRGs were obtained from the FerrDb database. An FRG prognostic index (FRGPI) was created using the minor absolute shrinkage and selection operator (LASSO)–Cox regression. The predictive ability of the FRGPI was validated in the GEO cohort.Finally, we verified the expression of the hub genes and the activity of the ferroptosis inducer FIN56 in GC cell lines and tissues. Results: Four hub genes were identified (NOX4, MTCH1, GABARAPL2, and SLC2A3) and shown to predict GC and H. pylori-associated GC accurately. The FRGPI based on the hub genes could independently predict GC patient survival; GC patients in the high-risk group had considerably worse OS than those in the low-risk group. The FRGPI was a significant predictor of GC prognosis and highly related to disease progression. Moreover, common immune checkpoint proteins (ICPs) gene expression levels dramatically increased in the FRGPI high-risk group.Additionally, the hub genes were confirmed to be highly overexpressed in GC cell lines and tissues and primarily localized at the cell membrane. The ferroptosis inducer FIN56 inhibited GC cell proliferation in a dose-dependent manner.