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

Abstract

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

CLC Number:

R735.3

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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Application of DNA methylation risk scoring model for ferroptosis related genes in the prognosis and immune feature assessment of colon cancer

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