Abstract
Hepatocellular carcinoma (HCC) is one of the world's malignant tumors with high morbidity and mortality. Cuproptosis is a novel form of cell death. However, the prognostic evaluation and immune relevance of cuproptosis-related genes (CRGs) in HCC are largely unknown. In our study, we constructed a prognostic model of CRGs in HCC and performed immune infiltration, functional analysis, immune checkpoint and drug sensitivity analysis. Systematically elaborated the prognostic and immune correlation of CRGs in HCC. The results showed that 15 CRGs were up-regulated or down-regulated in HCC, and the mutation frequency of CRGs reached 10.33% in HCC, with CDKN2A having the highest mutation frequency. These 19 CRGs were mainly involved in the mitochondrion, immune response and metabolic pathways. Five selected genes (CDKN2A, DLAT, DLST, GLS, PDHA1) were involved in constructing a prognostic CRGs model that enables the overall survival in HCC patients to be predicted with moderate to high accuracy. Prognostic CRGs, especially CDKN2A, the independent factor of HCC prognosis, may be closely associated with immune-cell infiltration, tumor mutation burden (TMB), microsatellite instability(MSI), and immune checkpoints. CD274, CTLA4, LAG3, PDCD1, PDCD1LG2 and SIGLEC15 may be identified as potential therapeutic targets and CD274 correlated highly with prognostic genes. Quantitative Real-Time PCR (qRT-PCR) and immunohistochemical were performed to validate the mRNA and protein expression levels of CDKN2A in adjacent normal tissues and HCC tissues, and the results were consistent with gene difference analysis. In conclusion, CRGs, especially CDKN2A, may serve as potential prognostic predictors in HCC patients and provide novel insights into cancer therapy.