A novel cuproptosis-related gene signature for overall survival prediction in patients with hepatocellular carcinoma

Prognosis prediction is difficult in hepatocellular carcinoma (HCC) due to high heterogeneity and complex etiology. It has recently been discovered that cuproptosis is a type of programmed cell death. However, its significance for HCC is still unclear. We analyzed mRNA expression profiles and clinical information from public databases to determine whether cuproptosis-related genes are associated with improved prognoses for HCC patients. The training cohort consisted of HCC patients from The Cancer Genome Atlas (TCGA), and the validation cohort relied on the International Cancer Genome Consortium (ICGC) database. We constructed a signature containing four genes using the least absolute shrinkage and selection operator (LASSO) COX regression model for calculating risk scores. Two risk groups were formed based on the median score. A significant improvement in survival was observed in the low-risk group compared to the high-risk. The multivariate Cox regression analysis showed that the risk score was an independent predictor of overall survival (OS). Further confirmation of the predictive accuracy of this signature is provided by receiver operating characteristic (ROC) analysis. Functional analysis revealed differences in immune status between the two risk groups. All the results described above were confirmed in the validation cohort. Therefore, a novel cuproptosis-related signature has the potential as a prognostic biomarker for HCC patients. Drugs developed to target cuproptosis-related genes may open up new pathways for treating HCC.