在结肠癌中,鉴定基于铜死亡作用的分子亚型,构建预测性标志,并表征免疫景观。
Identification of cuproptosis-based molecular subtypes, construction of prognostic signature and characterization of immune landscape in colon cancer.
发表日期:2023
作者:
Xu Wang, Xiaomin Zuo, Xianyu Hu, Yuyao Liu, Zhenglin Wang, Shixin Chan, Rui Sun, Qijun Han, Zhen Yu, Ming Wang, Huabing Zhang, Wei Chen
来源:
Burns & Trauma
摘要:
赛普罗瘤死是一种新发现的细胞死亡形式,它是通过靶向三羧酸循环中涉及的脂肪酰化蛋白质诱导的。然而,赛普罗瘤死相关基因(CRGs)在结肠癌的临床结果和免疫景观中的作用仍未知。我们对来自前一研究中确定的13个CRGs的表达数据和来自The Cancer Genome Atlas和Gene Expression Omnibus数据库的结肠癌患者的临床信息进行了生物信息学分析。结肠癌病例分为两个CRG簇和与预后相关的差异表达基因。患者数据分为三个相应的不同基因簇,并分析了风险评分、患者预后和免疫景观之间的关系。确定的分子亚型与患者生存、免疫细胞和免疫功能相关联。基于五个基因的预后标志被确定,根据计算得出的风险评分将患者分为高风险和低风险组。基于风险评分和其他临床特征,开发了预测患者生存的诊断模型。高风险组显示出更差的预后,风险评分与免疫细胞丰度、微卫星不稳定性、癌症干细胞指数、检查点表达、免疫逃逸以及对化疗药物和免疫疗法的反应有关。风险评分相关的发现在接受抗程序性细胞死亡配体1治疗的转移性膀胱癌患者的imvigor210队列中得到验证。我们展示了基于赛普罗瘤死的分子亚型和预后标志预测结肠癌患者生存和肿瘤微环境的潜力。我们的发现可能会改善对赛普罗瘤死在结肠癌中的作用的理解,并导致开发更有效的治疗策略。版权所有©2023年王,左郎,胡,刘,王,陈,孙,韩,于,王,张和陈。
Cuproptosis is a newly discovered form of cell death induced by targeting lipoacylated proteins involved in the tricarboxylic acid cycle. However, the roles of cuproptosis-related genes (CRGs) in the clinical outcomes and immune landscape of colon cancer remain unknown.We performed bioinformatics analysis of the expression data of 13 CRGs identified from a previous study and clinical information of patients with colon cancer obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. Colon cancer cases were divided into two CRG clusters and prognosis-related differentially expressed genes. Patient data were separated into three corresponding distinct gene clusters, and the relationships between the risk score, patient prognosis, and immune landscape were analyzed. The identified molecular subtypes correlated with patient survival, immune cells, and immune functions. A prognostic signature based on five genes was identified, and the patients were divided into high- and low-risk groups based on the calculated risk score. A nomogram model for predicting patient survival was developed based on the risk score and other clinical features.The high-risk group showed a worse prognosis, and the risk score was related to immune cell abundance, microsatellite instability, cancer stem cell index, checkpoint expression, immune escape, and response to chemotherapeutic drugs and immunotherapy. Findings related to the risk score were validated in the imvigor210 cohort of patients with metastatic urothelial cancer treated with anti-programmed cell death ligand 1.We demonstrated the potential of cuproptosis-based molecular subtypes and prognostic signatures for predicting patient survival and the tumor microenvironment in colon cancer. Our findings may improve the understanding of the role of cuproptosis in colon cancer and lead to the development of more effective treatment strategies.Copyright © 2023 Wang, Zuo, Hu, Liu, Wang, Chan, Sun, Han, Yu, Wang, Zhang and Chen.