Wang Xu, Zuo Xiaomin, Hu Xianyu, Liu Yuyao, Wang Zhenglin, Chan Shixin, Sun Rui, Han Qijun, Yu Zhen, Wang Ming, Zhang Huabing, Chen Wei
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Front Oncol. 2023 Mar 17;13:927608. doi: 10.3389/fonc.2023.927608. eCollection 2023.
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.
铜死亡是一种新发现的细胞死亡形式，由靶向参与三羧酸循环的脂酰化蛋白诱导产生。然而，铜死亡相关基因（CRGs）在结肠癌临床结局和免疫格局中的作用仍不清楚。
我们对先前研究中鉴定出的13个CRGs的表达数据以及从癌症基因组图谱和基因表达综合数据库获得的结肠癌患者临床信息进行了生物信息学分析。将结肠癌病例分为两个CRG簇和与预后相关的差异表达基因。将患者数据分为三个相应的不同基因簇，并分析风险评分、患者预后和免疫格局之间的关系。确定与患者生存、免疫细胞和免疫功能相关的分子亚型。鉴定出基于五个基因的预后特征，并根据计算出的风险评分将患者分为高风险组和低风险组。基于风险评分和其他临床特征建立了预测患者生存的列线图模型。
高风险组预后较差，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治疗的反应有关。在接受抗程序性细胞死亡配体1治疗的转移性尿路上皮癌患者的imvigor210队列中验证了与风险评分相关的结果。
我们证明了基于铜死亡的分子亚型和预后特征在预测结肠癌患者生存和肿瘤微环境方面的潜力。我们的研究结果可能会增进对铜死亡在结肠癌中作用的理解，并导致开发更有效的治疗策略。
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