Cuproptosis scoring system to predict the clinical outcome and immune response in bladder cancer.
Cuproptosis scoring system to predict the clinical outcome and immune response in bladder cancer.
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DOI：
10.3389/fimmu.2022.958368
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发表时间：
2022
影响因子：
7.3
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中科院分区：
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铜中毒是细胞内一种新型的铜离子依赖性细胞死亡类型，与细胞凋亡、细胞焦亡、坏死性凋亡、铁死亡等常见的细胞死亡模式有很大不同。有趣的是，与死亡模式一样，最近报道铜凋亡相关基因可以调节各种肿瘤的发生和进展。然而，在膀胱癌中，铜凋亡与临床结果、肿瘤微环境 (TME) 改变和免疫治疗之间的联系尚不清楚。为了确定铜死亡在肿瘤微环境中的作用，我们系统地检查了膀胱癌（BLCA）中 10 个铜死亡相关基因的特征模式。通过分析主成分数据，我们建立了铜凋亡评分来确定患者的铜凋亡程度。最后，我们评估了这些值在预测 BLCA 预后和治疗反应方面的潜力。在基因水平上对 BLCA 标本中铜凋亡相关基因的突变进行了全面研究，并使用癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 评估了它们的表达和生存模式。基于 10 个铜凋亡相关基因的转录水平构建了两种铜凋亡模式，其特征在于铜凋亡与 TME 之间的相互作用导致免疫细胞（特别是 T 细胞和树突状细胞）的预后和浸润景观存在差异。我们的研究进一步证明，铜凋亡评分可以预测膀胱癌患者的预后、化疗的免疫表型敏感性以及免疫治疗反应。膀胱癌的发生和进展很可能受到铜凋亡的影响，这可能涉及多样且复杂的 TME。我们的研究中评估的铜凋亡模式可能会增强对免疫浸润的理解并指导更有效的免疫治疗干预措施。
Cuproptosis is a novel copper ion-dependent cell death type being regulated in cells, and this is quite different from the common cell death patterns such as apoptosis, pyroptosis, necroptosis, and ferroptosis. Interestingly, like with death patterns, cuproptosis-related genes have recently been reported to regulate the occurrence and progression of various tumors. However, in bladder cancer, the link between cuproptosis and clinical outcome, tumor microenvironment (TME) modification, and immunotherapy is unknown. To determine the role of cuprotosis in the tumor microenvironment, we systematically examined the characteristic patterns of 10 cuproptosis-related genes in bladder cancer (BLCA). By analyzing principal component data, we established a cuproptosis score to determine the degree of cuproptosis among patients. Finally, we evaluated the potential of these values in predicting BLCA prognosis and treatment responses. A comprehensive study of the mutations of cuproptosis-related genes in BLCA specimens was conducted at the genetic level, and their expression and survival patterns were evaluated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Two cuproptosis patterns were constructed based on the transcription level of 10 cuproptosis-related genes, featuring differences in the prognosis and the infiltrating landscape of immune cells (especially T and dendritic cells) with interactions between cuproptosis and the TME. Our study further demonstrated that cuproptosis score may predict prognosis, immunophenotype sensitivity to chemotherapy, and immunotherapy response among bladder cancer patients. The development and progression of bladder cancer are likely to be influenced by cuproptosis, which may involve a diverse and complex TME. The cuproptosis pattern evaluated in our study may enhance understanding of immune infiltrations and guide more potent immunotherapy interventions.