Bioinformatics prediction and experimental verification identify a cuproptosis-related gene signature as prognosis biomarkers of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) of which its prognostic prediction is still unclarified is a highly heterogeneous disease. Cuproptosis is a form of cell death that depends on copper regulation. Whether the cuproptosis-related genes can be the prognostic indicators of HCC is yet to be elucidated. The aim of this study is to investigate whether cuproptosis-related genes play a role in HCC and can be used as a diagnostic index to predict the occurrence of liver cancer.

Methods: We downloaded HCC patients' gene expression profiles and their corresponding clinical data from a public database. To screen data, we used single factor Cox regression analysis, meanwhile, polymerase chain reaction (PCR) was used for the verification. After that, the risk score was calculated and the relationship between risk score and clinical factors was analyzed. Besides, a nomogram map was constructed for predicting the prognosis of HCC, and calibration map and decision curve analysis (DCA) map were used to test the model.

Results: Compared to the high expression group of four cuproptosis-related genes, the low expression group showed better overall survival (OS) [hazard ratio (HR) =2.58; 95% confidence interval (CI): 1.72-3.89, P<0.01]. The expression of the four cuproptosis-relate genes increased in liver cancer cell lines compared to liver cell lines (P<0.05). Based on these four genes, we calculated the risk score and divided them into two groups as high-risk group and low-risk group. The risk factor map showed the high-risk group had shorter survival time and the four genes were highly expressed. The area under curve (AUC) of receiver operating characteristic (ROC) prediction curve for the first year was 0.726. Risk scores were closely related to clinical factors and immune cells. Finally, we constructed a nomogram for predicting the prognosis of HCC.

Conclusions: The risk score for cuproptosis-related genes was established and involved in the construction of the nomogram, providing a new perspective on the prognosis and copper metabolism of HCC.