肝细胞癌（HCC）是一种高度异质性的疾病，其预后预测仍不清楚。铜中毒是一种依赖于铜调节的细胞死亡形式。铜凋亡相关基因是否可以作为HCC的预后指标尚待阐明。本研究的目的是探讨铜凋亡相关基因是否在HCC中发挥作用，并可作为预测肝癌发生的诊断指标。我们从公众网站下载了HCC患者的基因表达谱及其相应的临床数据。数据库。筛选数据时采用单因素Cox回归分析，同时采用聚合酶链式反应（PCR）进行验证。之后计算风险评分并分析风险评分与临床因素的关系。此外，构建了预测HCC预后的列线图，并利用校准图和决策曲线分析（DCA）图对模型进行了测试。与4个铜凋亡相关基因的高表达组相比，低表达组显示更好的总生存期 (OS) [风险比 (HR) =2.58； 95%置信区间（CI）：1.72-3.89，P<0.01]。与肝细胞系相比，肝癌细胞系中四种铜凋亡相关基因的表达增加（P<0.05）。根据这四个基因，我们计算了风险评分，并将它们分为两组：高风险组和低风险组。危险因素图显示高危组生存时间较短，且4个基因高表达。第一年受试者工作特征（ROC）预测曲线的曲线下面积（AUC）为0.726。风险评分与临床因素和免疫细胞密切相关。最后，我们构建了预测HCC预后的列线图。建立了铜凋亡相关基因的风险评分，并参与了列线图的构建，为HCC的预后和铜代谢提供了新的视角。2024转化癌症研究。版权所有。

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.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.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.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.2024 Translational Cancer Research. All rights reserved.