铜的异常积累可诱导细胞死亡和肿瘤生长，并通过调节程序性细胞死亡配体1（PD-L1）的表达影响肿瘤免疫逃逸。本研究旨在建立和验证基于铜凋亡和免疫相关基因 (CIRG) 的肝细胞癌 (HCC) 管理风险特征。HCC RNA-seq 和临床数据来自开放数据库。利用最小绝对收缩和选择算子 (LASSO) 和 Cox 回归分析来筛选 CIRG 并开发风险特征。系统地研究了该签名的临床应用价值、功能丰富、肿瘤突变负担（TMB）和免疫谱分析。利用七个 CIRG 开发了风险签名，在预测 HCC 患者的训练和预后方面均表现良好。外部验证队列。研究发现该模型的风险评分与重要的临床特征相关。 HCC 中前 15 个突变基因在不同风险组之间存在显着差异。高危患者的 TMB 较高，高 TMB 与预后较差密切相关。免疫谱分析显示，低危患者的免疫浸润水平高于高危患者，且两个不同风险组患者之间免疫检查点基因表达水平存在显着差异。低风险患者对免疫治疗反应良好，而高风险患者对索拉非尼、阿霉素、吉西他滨和AKT（又称蛋白激酶B）抑制剂更敏感。基于CIRG建立的风险特征不仅可以很好地预测预后HCC 患者的治疗，但在评估 TMB 以及对免疫疗法、靶向治疗和化疗的治疗反应方面也很有希望，这有可能协助 HCC.2024 转化癌症研究的临床管理。版权所有。

Abnormal accumulation of copper could induce cell death and tumor growth, and affect tumor immune escape by regulating programmed cell death ligand 1 (PD-L1) expression. This study aims to establish and verify a risk signature based on cuproptosis- and immune-related genes (CIRGs) for hepatocellular carcinoma (HCC) management.HCC RNA-seq and clinical data were obtained from open databases. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were utilized to screen CIRGs and develop a risk signature. The signature's value for clinical applications, functional enrichment, tumor mutation burden (TMB), and immune profile analyses were investigated systematically.A risk signature was developed utilizing seven CIRGs, and it performed well in predicting the prognosis of HCC patients in both the training and external validation cohorts. The model's risk score was discovered to be related to important clinical features. Top 15 mutated genes in HCC were significantly different among different risk groups. High-risk patients showed higher TMB, and high TMB was closely identified with a poorer prognosis. Immune profile analyses showed that immune infiltration level was higher in low-risk patients than high-risk patients, and the level of immune checkpoint genes expression varied significantly between patients in two different risk groups. Low-risk patients responded well to immunotherapy treatment, whereas high-risk patients were more sensitive to sorafenib, doxorubicin, gemcitabine and AKT (also known as protein kinase B) inhibitors.The established risk signature based on CIRGs can not only well predict the prognosis of HCC patients but is also promising in evaluating TMB and treatment response to immunotherapy, targeted therapy and chemotherapy, which has the potential to assist in the clinical management of HCC.2024 Translational Cancer Research. All rights reserved.