He Yinghao, Liu Fuqiang, Li Qingshu, Jiang Zheng
Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Gastroenterology, The People's Hospital of Jianyang City, Jianyang, Sichuan Province, China.
PLoS One. 2025 Jan 30;20(1):e0307013. doi: 10.1371/journal.pone.0307013. eCollection 2025.
Colon cancer, as a highly prevalent malignant tumor globally, poses a significant threat to human health. In recent years, ferroptosis and cuproptosis, as two novel forms of cell death, have attracted widespread attention for their potential roles in the development and treatment of colon cancer. However, the investigation into the subtypes and their impact on the survival of colon cancer patients remains understudied. In this study, utilizing data from TCGA and GEO databases, we examined the expression differences of ferroptosis and cuproptosis-related genes in colon cancer and identified two subtypes. Through functional analysis and bioinformatics methods, we elucidated pathway differences and biological characteristics between these two subtypes. By leveraging differential genes between the two subtypes, we constructed a prognostic model using univariate Cox regression and multivariate Cox regression analysis as well as LASSO regression analysis. Further survival analysis and receiver operating characteristic curve analysis demonstrated the model's high accuracy. To enhance its clinical utility, we evaluated the clinical significance of the model and constructed a nomogram, significantly improving the predictive ability of the model and providing a new tool for prognostic assessment of colon cancer patients. Subsequently, through immune-related analysis, we revealed differences in immune cell infiltration and immune function between high- and low-risk groups. Further analysis of the relationship between the model and immune cells and functions revealed potential therapeutic targets. Drug sensitivity analysis revealed associations between the expression of model-related genes and drug sensitivity, suggesting their involvement in tumor resistance through certain mechanisms. AZD8055_1059, Bortezomib_1191, Dihydrorotenone_1827, and MG-132_1862 were more sensitive in the high-risk group. Finally, we analyzed differential expression of model-related genes between tumor tissues and normal tissues, validated through real-time quantitative PCR and immunohistochemistry. In summary, our study provides a relatively accurate prognostic tool for colon cancer patients, offering guidance for treatment selection and indicating the potential of immunotherapy in colon cancer.
结肠癌作为全球一种高度流行的恶性肿瘤，对人类健康构成重大威胁。近年来，铁死亡和铜死亡作为两种新型细胞死亡形式，因其在结肠癌发生发展及治疗中的潜在作用而受到广泛关注。然而，对结肠癌亚型及其对患者生存影响的研究仍不充分。在本研究中，我们利用来自TCGA和GEO数据库的数据，检测了结肠癌中铁死亡和铜死亡相关基因的表达差异，并鉴定出两种亚型。通过功能分析和生物信息学方法，我们阐明了这两种亚型之间的通路差异和生物学特征。利用两种亚型之间的差异基因，我们通过单变量Cox回归、多变量Cox回归分析以及LASSO回归分析构建了一个预后模型。进一步的生存分析和受试者工作特征曲线分析表明该模型具有很高的准确性。为提高其临床实用性，我们评估了该模型的临床意义并构建了列线图，显著提高了模型的预测能力，为结肠癌患者的预后评估提供了一种新工具。随后，通过免疫相关分析，我们揭示了高风险组和低风险组之间免疫细胞浸润和免疫功能的差异。对模型与免疫细胞及功能之间关系的进一步分析揭示了潜在的治疗靶点。药物敏感性分析揭示了模型相关基因的表达与药物敏感性之间的关联，表明它们通过某些机制参与肿瘤耐药。AZD8055_1059、硼替佐米_1191、二氢鱼藤酮_1827和MG - 132_1862在高风险组中更敏感。最后，我们分析了肿瘤组织和正常组织之间模型相关基因的差异表达，并通过实时定量PCR和免疫组织化学进行了验证。总之，我们的研究为结肠癌患者提供了一种相对准确的预后工具，为治疗选择提供指导，并表明免疫疗法在结肠癌中的潜力。
