Development and Validation of the novel Cuproptosis- and Immune-related Signature for Predicting Prognosis in Hepatocellular Carcinoma.

: Hepatocellular carcinoma often results in late-stage diagnosis, leading to decreased treatment success. To improve prognosis, this study integrates cuproptosis with immune risk scoring models for HCC patients. We identified differentially expressed genes connected to cuproptosis and immune responses using Pearson correlation. A risk signature was then constructed via LASSO regression, and its robustness was validated in the International Cancer Genome Consortium dataset. Additionally, qPCR confirmed findings in tumor and normal tissues. : Eight genes emerged as key prognostic markers from the 110 differentially expressed genes linked to cuproptosis and immunity. A risk-scoring model was developed using gene expression, effectively categorizing patients into low- or high-risk groups. Validated in the ICGC dataset, high-risk patients had significantly reduced survival times. Multivariate Cox regression affirmed the risk signature's independent predictive capability. A clinical nomogram based on the risk signature was generated. Notably, low-risk patients might benefit more from immune checkpoint inhibitors. qPCR and western blotting results substantiated our bioinformatics findings. : The genetic risk signature linked to cuproptosis and immunity holds potential as a vital prognostic biomarker for Hepatocellular carcinoma, providing avenues for tailored therapeutic strategies.