Clinical College, Wuhan University of Science and Technology, Wuhan 430000, China.
Tianyou Hospital of Wuhan University of Science and Technology, Wuhan 430000, China.
Comb Chem High Throughput Screen. 2023;26(8):1578-1593. doi: 10.2174/1386207326666230120112904.
Copper-induced death (cuproptosis) is copper-dependent regulated cell death, which is different from known death mechanisms and is dependent on mitochondrial respiration. However, its effect on breast cancer (BRCA) is unclear.
The objective of this study is to explore the important clinical significance of cuproptosis genes and to provide a new idea for guiding the personalized immunotherapy strategy of BRCA patients.
We collected cuproptosis genes from published work. The gene alteration, differential expression, and prognostic value of cuproptosis genes were explored in BRCA based on TCGA database. We identified two subtypes (clusters A and B) by performing unsupervised clustering. The difference between two clusters was deeply explored, including clinical features, differential expressed genes (DEGs), pathways, and immune cell infiltration. Based on the DEGs between two clusters, a cuproptosis score was constructed and its predictive capability for overall survival of BRCA patients was validated.
Patients with high cuproptosis score have worse survival status, with an increased infiltration level of most immune cells. Further analysis suggested that BRCA patients with high cuproptosis score may be sensitive to immune checkpoint inhibitor (ICI) treatment.
Our findings may improve our understanding of cuproptosis in BRCA and may distinguish patients suitable for ICI treatment.
铜诱导的死亡（cuproptosis）是一种依赖铜的调控细胞死亡，与已知的死亡机制不同，依赖于线粒体呼吸。然而，其对乳腺癌（BRCA）的影响尚不清楚。
本研究旨在探讨 cuproptosis 基因的重要临床意义，为指导 BRCA 患者的个性化免疫治疗策略提供新的思路。
我们从已发表的研究中收集了 cuproptosis 基因。基于 TCGA 数据库，探讨了 cuproptosis 基因在 BRCA 中的基因改变、差异表达和预后价值。我们通过无监督聚类方法识别了两个亚组（簇 A 和 B）。深入探讨了两个亚组之间的差异，包括临床特征、差异表达基因（DEGs）、通路和免疫细胞浸润。基于两个亚组之间的 DEGs，构建了 cuproptosis 评分，并验证了其对 BRCA 患者总生存的预测能力。
高 cuproptosis 评分的患者生存状态较差，大多数免疫细胞的浸润水平增加。进一步分析表明，高 cuproptosis 评分的 BRCA 患者可能对免疫检查点抑制剂（ICI）治疗敏感。
我们的发现可能提高对 BRCA 中 cuproptosis 的认识，并区分适合 ICI 治疗的患者。
