Analysis of novel therapeutic targets and construction of a prognostic model for hepatocellular carcinoma.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) remains suboptimal due to limited biomarkers. Although ferroptosis and cuproptosis have emerged as promising therapeutic targets, their prognostic significance in HCC remains unclear. METHODS: This study analyzed the expression of ferroptosis- and cuproptosis-related genes associated with survival in HCC, utilizing datasets from The Cancer Genome Atlas and the Gene Expression Omnibus. The impact of clinical factors on patient prognosis was also analyzed. The key findings were validated using the Human Protein Atlas database, quantitative real-time PCR, and Western blot (WB) analyses. RESULTS: Prognostic modeling identified six ferroptosis-related genes (SLC1A5, SLC7A11, CBS, GABARAPL1, FLT3, and MT3) and three cuproptosis-related genes (ADM, CDKN2A, and GLS) significantly associated with HCC prognosis. A robust risk assessment model was developed with strong predictive power. The inflammatory cell apoptotic process is an immune-related pathway that is commonly enriched by ferroptosis and cuproptosis genes. Immune cell profiling using CIBERSORT revealed significant differences in macrophages, naive B cells, mast cells, monocytes, memory CD4+ T cells, and CD8+ T cells. CONCLUSIONS: This study, for the first time, integrated multi-omics data and experimental verification to establish a prognostic model of HCC based on the ferroptosis gene. It can be used to dynamically monitor HCC using blood tests and provide a new target for personalized immunotherapy.