Identification of cuproptosis-related gene CDKN2A as a molecular diagnostic target in gastric carcinoma based on transcriptomic data

Gastric Carcinoma (GC) is the world’s third-highest cause of death by cancer. Cuproptosis is a newly discovered programmed cell death dependent on overload copper-induced mitochondrial respiration dysregulation. We speculated this regulatory cell death (RCD) mechanism might serve as a potential prognostic predictors and therapy for GC patients. The expression and mutation patterns of 12 cuproptosis-related genes were systematically evaluated in the GC training group. Through unsupervised clustering analysis and developing a cuproptosis-related scoring system, we further explored the relationship between cuproptosis and GC progression, prognosis, immune cell infiltration, and immunotherapy. Molecular docking was used to screen the drugs which had the best binding affinity with cuproptosis target proteins. CCK8, invasion and migration assay were used to explore the anticancer effect of the drug which binging to the cuproptosis target protein and then verify it in nudes. Our results revealed three genes (CDKN2A, GLS, and MTF1) have predictive value for the prognosis. Patients from low-CRG score group were characterized by higher immune cell infiltration, immune checkpoint expression. Via molecular docking, CCK8, invasion and migration assay, saquinavir had the best binding affinity with CDKN2A,which could inhibit the proliferation, invasion, and migration of gastric carcinoma cells in vitro. Ani-mal experiment showed that saquinavir treated group had smaller volume and weight tumors. Our results confirmed the essential function of cuproptosis in regulating the progression, prognosis, immune cell infiltration, and response to immunotherapy. CDKN2A as the potential target for gastric carcinoma showed the anticancer effect in vitro and vivo.