Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; The Hunan Provincial Key Lab of Precision Diagnosis and Treatment for Gastrointestinal Tumor, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; The Hunan Provincial Key Lab of Precision Diagnosis and Treatment for Gastrointestinal Tumor, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Int Immunopharmacol. 2024 Sep 30;139:112798. doi: 10.1016/j.intimp.2024.112798. Epub 2024 Jul 29.
The aim of this study was to construct a prognostic model of colon cancer based on demethylation-related genes. An in-depth understanding of the relationship between the set of demethylated genes and colon cancer not only assists in revealing the pathogenesis of colon cancer but also provides strong support for future therapeutic strategies and individualized medicine.
Data were obtained from the TCGA database and the GEO-GSE39582 cohort. A risk score model for demethylation-related genes was developed using univariate Cox regression analysis and LASSO regression analysis. The accuracy and reliability of the model were confirmed using K-M survival analysis and ROC curve analysis. Additionally, a nomogram was created by integrating the risk score and clinicopathological variables. Finally, the biological function of the RCOR2 gene was verified by performing qPCR, MTT, colony formation, Transwell, and subcutaneous tumor formation assays in nude mice.
We constructed a risk score model containing 30 demethylation-related genes for predicting the survival risk of patients with colon cancer. COAD patients were categorized into high-risk and low-risk groups, and Kaplan-Meier (KM) curve analysis revealed that the high-risk group was associated with a worse prognosis. Univariate and multivariate Cox regression analyses validated the risk score as an independent prognostic factor for COAD. We also analyzed the differences in the sensitivity to nine chemotherapeutic agents and small molecule targeted drugs between the high-risk and low-risk groups. Moreover, we performed experiments in COAD cell lines and nude mice to verify that RCOR2 was differentially expressed between tumor tissues and normal tissues and that high RCOR2 expression promoted a malignant phenotype of colon cancer.
This study demonstrated the potential roles of demethylation-related genes in colon cancer by conducting a comprehensive analysis and constructing a risk score. These findings also highlight the ability of these genes to indicate patient prognosis and tumor immune microenvironment. Furthermore, this study provides a reliable predictive tool that can assist in guiding the treatment and management of colon cancer patients.
本研究旨在构建基于去甲基化相关基因的结肠癌预后模型。深入了解这组去甲基化基因与结肠癌之间的关系，不仅有助于揭示结肠癌的发病机制，而且为未来的治疗策略和个体化医学提供了有力支持。
从 TCGA 数据库和 GEO-GSE39582 队列中获取数据。使用单因素 Cox 回归分析和 LASSO 回归分析构建去甲基化相关基因风险评分模型。通过 K-M 生存分析和 ROC 曲线分析验证模型的准确性和可靠性。此外，通过整合风险评分和临床病理变量创建了列线图。最后，通过在裸鼠中进行 qPCR、MTT、集落形成、Transwell 和皮下肿瘤形成实验验证 RCOR2 基因的生物学功能。
我们构建了一个包含 30 个去甲基化相关基因的风险评分模型，用于预测结肠癌患者的生存风险。COAD 患者分为高风险和低风险组，Kaplan-Meier（KM）曲线分析显示，高风险组预后较差。单因素和多因素 Cox 回归分析验证了风险评分是 COAD 的独立预后因素。我们还分析了高风险和低风险组对 9 种化疗药物和小分子靶向药物的敏感性差异。此外，我们在 COAD 细胞系和裸鼠中进行了实验，验证了 RCOR2 在肿瘤组织和正常组织之间的表达差异，并且高 RCOR2 表达促进了结肠癌的恶性表型。
本研究通过全面分析和构建风险评分，展示了去甲基化相关基因在结肠癌中的潜在作用。这些发现还强调了这些基因在指示患者预后和肿瘤免疫微环境方面的能力。此外，本研究提供了一种可靠的预测工具，可以帮助指导结肠癌患者的治疗和管理。
