铁死亡相关基因的DNA甲基化风险评分模型在结肠癌预后与免疫特征评估中的应用

doi:10.11904/j.issn.1002-3070.2025.03.008

摘要/Abstract

摘要： 目的本研究旨在构建基于铁死亡相关基因的DNA甲基化特征的风险评分模型,评估其对结肠癌患者预后及免疫治疗响应的预测价值。方法本研究基于TCGA和GEO数据库获取结肠癌患者的转录组、DNA甲基化及临床数据。通过FerrDb数据库获取铁死亡相关基因,利用ssGSEA计算每位患者的铁死亡评分(ferroptosis score,FS),结合差异甲基化CpG位点与Cox回归分析构建风险评分模型。通过ROC曲线、列线图和决策曲线分析评估模型性能。利用多种算法分析结肠癌模型与免疫细胞浸润、免疫治疗反应及化疗敏感性之间的关系。结果共筛选出49个与总生存期(overall survival,OS)显著相关的铁死亡基因用于计算FS。高FS组患者OS显著短于低FS组(P=0.0075)。构建的甲基化风险模型包含关键CpG位点,在TCGA队列,验证队列GSE17536中1年、3年和5年总生存率的ROC曲线和多因素Cox回归分析显示该模型为结肠癌患者的独立预后因子。低风险组具有更高的免疫评分以及B细胞、树突状细胞的浸润水平,而高风险组中成纤维细胞丰度更高。高风险组患者PD-L1表达上调,免疫表型评分更高。此外,该模型还可预测阿霉素、吉西他滨、紫杉醇等常用化疗药物的敏感性差异。结论利用铁死亡相关基因的DNA甲基化特征建立的风险评分模型,可用来预测结肠癌患者的预后,并且为实现精准治疗提供一种新的生物标志物。

关键词: 铁死亡, DNA甲基化, 结肠癌, 肿瘤微环境

Abstract: Objective This study aimed to construct a risk scoring model based on DNA methylation featuresof ferroptosis-related gene,and systematically evaluate its predictive value for the prognosis and immunotherapy response of patients with colon cancer. Methods Transcriptomic,DNA methylation,and clinical data of colon cancer patients were obtained from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Ferroptosis-related genes were identified from the FerrDb database.Ferroptosis scores(FS)for each patient were calculated using the single-sample gene set enrichment analysis(ssGSEA)method,and construct a risk scoring model by combining differential methylation CpG sites with Cox regression analysis.The prognostic performance of the model was evaluated using receiver operating characteristic(ROC)curves,a nomogram,and decision curve analysis.The multiple algorithms were used to analyze the relationship between colon cancer models and immune cell infiltration,immunotherapy response,and chemotherapy sensitivity. Results A total of 49 ferroptosis-related genes significantly associated with overall survival(OS)were identified for calculating FS.The OS of colon cancer patients in the high-FS group was significantly shorter than that in the low-FS group(P=0.0075).The constructed DNA methylation risk score models included key CpG sites,and the ROC curves and multivariate Cox regression analysis at 1-,3-,and 5-years overall survival rate in the TCGA cohort and the GSE17536 validation cohort showed that the model was an independent prognostic factor for colon cancer patients.The low-risk group had higher immune scores and infiltration levels of B cells and dendritic cells,while the high-risk group had a higher abundance of fibroblasts.Patients in the high-risk group showed upregulation of PD-L1 expression and higher immune phenotype scores.In addition,the model could also predict the sensitivity differences of commonly used chemotherapeutic drugs such as doxorubicin,gemcitabine,and paclitaxel. Conclusion The risk scoring model established using DNA methylation features of ferroptosis-related gene can be used to predict the prognosis of colon cancer patients and provide a new biomarker for achieving precision treatment.

Key words: Ferroptosis, DNA methylation, Colon cancer, Tumor microenvironment

中图分类号:

R735.3

李冬生, 李泽昊, 陈永刚. 铁死亡相关基因的DNA甲基化风险评分模型在结肠癌预后与免疫特征评估中的应用[J]. 实用肿瘤学杂志, 2025, 39(3): 224-234.

LI Dongsheng, LI Zehao, CHEN Yonggang. Application of DNA methylation risk scoring model for ferroptosis related genes in the prognosis and immune feature assessment of colon cancer[J]. Journal of Practical Oncology, 2025, 39(3): 224-234.

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