MYC_V1-Related Genes Affect Gastric Cancer Proliferation by Regulating Energy Metabolism and Analysis of Therapeutic Targets.

Gastric cancer (GC) is the fifth leading cause of cancer-related mortality worldwide. Treatment options for advanced GC remain limited, owing to the frequent emergence of drug resistance. This highlights an urgent clinical need for novel therapeutic targets. Abnormal energy metabolism is a hallmark feature of cancer. MYC_V1-driven metabolic reprogramming plays a pivotal role in tumor progression. However, the specific mechanisms by which MYC_V1-related genes regulate energy metabolism in GC remains poorly understood. We employed single-sample gene set enrichment analysis (ssGSEA) to evaluate multiple tumor hallmarks in GC. A prognostic risk model was constructed based on MYC_V1-related genes, with the risk score (RS) used to stratify patients into distinct risk groups. A nomogram was developed and validated using calibration curves. Through the systematic molecular docking screening of 8327 compounds, potential therapeutic agents were identified. Functional experiments, including the CCK-8 assay, wound-healing assay and ATP production assay, were conducted to validate the role of NDUFV2 in GC progression. This study identified MYC_V1 as the primary risk factor affecting the overall survival (OS) in GC patients (p = 0.038). A prognostic risk model was successfully constructed based on eight MYC_V1-related genes (KPNA2, MCM2, MCM4, NDUFV2, PDK4, MPO, IGFBP1, and STC2). The RS was confirmed as an independent prognostic factor. The prognostic risk model accurately predicted patient 1-, 3-, and 5-year OS in GC patients. Tumor microenvironment analysis revealed significant differences in immune cell infiltration patterns between high-risk and low-risk groups. High-throughput drug screening and molecular docking identified camptothecin (CPT) and vinblastine as showing strong therapeutic potential for high-risk patients. Experimental validation demonstrated that NDUFV2 was significantly overexpressed in GC tissues, and its knockdown markedly suppressed the proliferation, migration capacity, and intracellular ATP production in GC cells, confirming the critical role of NDUFV2 in GC progression. These findings establish NDUFV2 as a potential therapeutic target in GC.