铜亲和性细胞凋亡（cuproptosis）是一种新报道的程序性细胞死亡类型，参与了多种疾病进展的过程。一些研究已经报道了在多种肿瘤中其潜在的重要性。结直肠癌（CRC）是发病率和死亡率较高的恶性肿瘤之一。本研究的目的是进一步探讨铜亲和性细胞凋亡在CRC发展和治疗中的重要性。我们分析了CRC患者中与铜亲和性细胞凋亡相关基因（CRGs）的表达、变异和启动子甲基化。我们使用了三种机器学习方法来确定与铜亲和性细胞凋亡相关的特征基因，并基于它们建立了一个诊断模型。通过无监督聚类，将CRC患者分为不同的簇。然后，我们使用LASSO方法建立了一个铜亲和性细胞凋亡风险模型。我们分析了风险评分与结果、免疫微环境、免疫治疗反应和化疗药物敏感性之间的关联。结果显示，CRGs在CRC中的表达发生了失调。基于铜亲和性细胞凋亡相关特征基因的诊断模型具有很大的临床价值。两个簇中的患者显示出不同的预后和微环境。此外，风险评分与临床特征、免疫浸润和免疫治疗、化疗的反应具有相关性。总之，本研究结果揭示了铜亲和性细胞凋亡在CRC发展中的参与，并提供了一个评估CRC发生风险的诊断工具。免疫浸润和药物敏感性分析结果有助于预测不同亚型CRC患者对免疫治疗和化疗的反应。© 2023 Wiley Periodicals LLC.

Cuproptosis is a newly reported type of programmed cell death that is involved in the progression of various diseases. Some studies have reported its potential significance in multiple tumors. Colorectal cancer (CRC) is one of the malignant tumors with high incidence and mortality. The purpose of this study was to further explore the importance of cuproptosis in the CRC development and treatment. We analyzed the expression, alterations, and promoter methylation of cuproptosis-related genes (CRGs) in patients with CRC. Three machine learning methods was used to determine cuproptosis-related feature genes and a diagnostic model was built based on them. Using the unsupervised clustering, patients with CRC were classified into distinct clusters. Then, the LASSO method was used to establish a cuproptosis risk model. We analyzed the association of risk scores with outcomes, immune microenvironment, response to immunotherapy, and sensitivity to chemotherapeutic drugs. The results showed that the expression of CRGs was dysregulated in CRC. The diagnostic model based on cuproptosis-related feature genes showed great clinical value. The patients in two clusters displayed different prognosis and microenvironment. Furthermore, the risk score was correlated with clinical characteristics, immune infiltration and response to immunotherapy and chemotherapy. Above all, the present findings revealed the involvement of cuproptosis in CRC development and provided a diagnostic tool to evaluate CRC occurrence risk. The immune infiltration and drug sensitivity analysis results helped to predict the response of patients in different subtypes of CRC to immunotherapy and chemotherapy.© 2023 Wiley Periodicals LLC.