背景：铜质细胞死亡是一种新型的调控性细胞死亡方式，据报道可以促进肿瘤的发生和进展。然而，铜质细胞死亡相关基因（CRGs）签名是否对肝细胞癌（HCC）有影响仍不清楚。材料与方法：我们分析了来自癌症基因组图谱（TCGA）和国际癌症基因组协调联盟（ICGC）数据库的HCC转录组数据，并通过一致性聚类法寻找具有不同铜质细胞死亡模式的肿瘤类型。然后，我们通过LASSO COX回归建立了一个基于CRGs的风险签名，并进一步分析其对HCC的预后、临床特征、免疫细胞浸润和药物敏感性的影响。结果：我们确定了HCC中10个与铜质细胞死亡相关基因的表达变化，通过应用一致性聚类算法，所有患者可被分为两个具有不同预后的亚型。然后我们构建了一个铜质细胞死亡相关风险签名，并确定了五个高度与预后相关且代表这个基因集的CRGs，即G6PD，PRR11，KIF20A，EZH2和CDCA8。低CRGs签名组患者的预后良好。我们进一步在ICGC队列中验证了CRGs签名，并得到一致的结果。此外，我们还发现CRGs签名与临床特征、不同的免疫景观和药物敏感性显著相关。此外，我们探索了高CRGs签名组对免疫治疗更为敏感的情况。结论：我们的综合分析展示了CRGs在HCC中的潜在分子标记和临床应用。基于CRGs的模型可以精确预测HCC的生存结果，并有助于更好地指导HCC患者的风险分层和治疗策略。版权所有©2023 He, Zeng, Ma, Yang, Liu, Liu, Zhou和Zhu。

Background: Cuproptosis is a novel type of regulated cell death and is reported to promote tumor occurrence and progression. However, whether a cuproptosis-related signature has an impact on hepatocellular carcinoma (HCC) is still unclear. Materials and methods: We analyzed the transcriptome data of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database, and searched for tumor types with different cuproptosis patterns through consistent clustering of cuproptosis genes. We then constructed a Cuproptosis-Related Genes (CRGs)-based risk signature through LASSO COX regression, and further analyzed its impact on the prognosis, clinical characteristics, immune cell infiltration, and drug sensitivity of HCC. Results: We identified the expression changes of 10 cuproptosis-related genes in HCC, and all the patients can be divided into two subtypes with different prognosis by applying the consensus clustering algorithm. We then constructed a cuproptosis-related risk signature and identified five CRGs, which were highly correlated with prognosis and representative of this gene set, namely G6PD, PRR11, KIF20A, EZH2, and CDCA8. Patients in the low CRGs signature group had a favorable prognosis. We further validated the CRGs signature in ICGC cohorts and got consistent results. Besides, we also discovered that the CRGs signature was significantly associated with a variety of clinical characteristics, different immune landscapes and drug sensitivity. Moreover, we explored that the high CRGs signature group was more sensitive to immunotherapy. Conclusion: Our integrative analysis demonstrated the potential molecular signature and clinical applications of CRGs in HCC. The model based on CRGs can precisely predict the survival outcomes of HCC, and help better guide risk stratification and treatment strategy for HCC patients.Copyright © 2023 He, Zeng, Ma, Yang, Liu, Liu, Zhou and Zhu.