乳腺癌（BRCA）是一种高度异质性的恶性肿瘤，迫切需要建立一个合适的模型来预测其预后。铜死亡是一种最近发现的细胞死亡方式，介导蛋白脂酰化并且与线粒体代谢密切相关。铜死亡相关基因（CRGs）在乳腺癌中的作用尚待探索。我们旨在通过对公共数据库中获取的信使RNA剖析和临床数据进行生物信息学分析，研究CRGs在不同临床情境中（包括化疗和免疫疗法）在乳腺癌预后中的应用。通过一致性聚类分析对CRGs进行了分子亚型划分。确定了不同CRG簇之间的差异表达基因。然后，利用最小二乘收缩选择算子回归使用差异表达基因构建了风险评估模型，以预测乳腺癌患者的生存。随后，使用来自乳腺癌分子分类国际联合会、GSE96058和GSE20685的数据对模型进行了验证。通过比较高风险组和低风险组，分析了体细胞突变、拷贝数变异、标志性通路、药物反应以及免疫疗法和化疗的预后差异。高风险评分的患者显示出更差的总体生存率。结果表明，两组间存在免疫相关生物学途径和不同的免疫状态。它还暗示了两组对化疗的敏感性差异。CRGs模型显示了预测乳腺癌患者预后的前景，并为其治疗提供了线索。版权所有 © 2023 作者。由 Wolters Kluwer Health, Inc. 发布。

Breast cancer (BRCA) is a highly heterogeneous malignancy with an urgent need to build a proper model to predict its prognosis. Cuproptosis is a recently discovered form of cell death, mediated by protein fatty acylation and tightly associated with mitochondrial metabolism. The role of cuproptosis-related genes (CRGs) in BRCA remains to be explored. We aimed to investigate the applications of CRGs in BRCA prognosis in different clinical contexts, including chemotherapy and immunotherapy, via bioinformatics analysis of the messenger RNA profiles and clinical data obtained from public databases. Molecular subtyping of CRGs was performed through consistent clustering analysis. Differentially expressed genes between different CRG clusters were identified. The differentially expressed genes were then used to build a risk assessment model using least absolute shrinkage and selection operator regression to predict patient survival with BRCA. The model was then validated with the data from the Molecular Taxonomy of Breast Cancer International Consortium, GSE96058, and GSE20685. Differences in somatic mutations, copy number variations, hallmark pathways, drug responses, and prognosis of immunotherapy and chemotherapy were analyzed by comparing the high-risk and low-risk groups. Patients with high-risk scores showed worse overall survival than those with low-risk scores. The results indicated significant differences between the 2 groups immune-related biological pathways and the variable immune status. It also suggests the differential sensitivity to chemotherapy between the 2 groups. The CRGs model showed the promise to predict the prognosis of BRCA patients and shed light on their treatment.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.