Center of Clinical Reproductive Medicine, Jinhua People's Hospital, Jinhua, Zhejiang Province, P. R. China.
Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, Jinhua, Zhejiang Province, P. R. China.
Medicine (Baltimore). 2023 Aug 4;102(31):e34507. doi: 10.1097/MD.0000000000034507.
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.
乳腺癌（BRCA）是一种高度异质性的恶性肿瘤，迫切需要建立适当的模型来预测其预后。铜死亡是一种新发现的细胞死亡形式，由蛋白质脂肪酸酰化介导，与线粒体代谢密切相关。铜死亡相关基因（CRGs）在 BRCA 中的作用仍有待探索。我们旨在通过对公共数据库中获得的信使 RNA 谱和临床数据进行生物信息学分析，研究 CRGs 在不同临床环境（包括化疗和免疫治疗）中在 BRCA 预后中的应用。通过一致聚类分析对 CRGs 进行分子亚型分析。鉴定不同 CRG 簇之间差异表达的基因。然后，使用最小绝对收缩和选择算子回归将差异表达基因用于构建风险评估模型，以预测具有 BRCA 的患者的生存情况。然后使用来自乳腺癌国际分子分类联盟、GSE96058 和 GSE20685 的数据验证该模型。通过比较高风险和低风险组，分析体细胞突变、拷贝数变异、标志性通路、药物反应和免疫治疗和化疗的预后差异。高风险评分的患者总生存率低于低风险评分的患者。结果表明，2 组之间存在显著差异免疫相关生物学途径和可变免疫状态。这也表明了 2 组之间对化疗的敏感性差异。CRGs 模型有望预测 BRCA 患者的预后，并为其治疗提供启示。
