基于铁死亡基因结肠癌分子预后模型的建立与分析

Establishment and analysis of a molecular prognostic model for colon cancer based on ferroptosis-related genes

目的分析结肠癌中铁死亡相关基因,构建基于铁死亡基因结肠癌分子预后模型。方法在癌症基因图谱数据库中下载结肠癌转录组测序数据和患者临床信息。采用R 4.1.0软件获取结肠癌患者相应铁死亡相关基因的表达数据并进行差异基因分析。使用功能富集分析差异基因参与的生物学作用和功能。结合患者生存资料,采用COX回归分析筛选出与患者预后相关的基因,构建风险评分方程。根据风险评分将结肠癌患者分为高、低风险组。利用受试者工作特征曲线评价预后模型的灵敏度和特异度。结果与正常组织比较,结肠癌组织中共有72个失调表达的铁死亡相关基因。差异基因主要参与了铁死亡及肿瘤相关信号通路。DRD4、TFAP2C、ENPP2、CAV14个铁死亡相关基因与患者预后相关(P<0.05),可用于风险预后模型的构建。与低风险组比较,高风险组患者总体生存率较差,差异有统计学意义(P<0.05)。基于铁死亡基因结肠癌分子预后模型预测患者1、3、5年生存率的曲线下面积分别为0.714、0.750、0.759,具有较好的灵敏度和特异度。结论基于铁死亡基因结肠癌分子预后模型成功构建,可较好地预测结肠癌患者的预后。

Objective To analyze the ferroptosis-related genes in colon cancer and construct a molecular prognostic model based on the expression of ferroptosis-related genes.Methods The transcriptome sequencing data of colon cancer and the clinical information of patients were downloaded from the Cancer Genome Atlas(TCGA)database.The R 4.1.0 software was used to obtain the expression data of the ferroptosis-related genes and the differential genes were analyzed.The functional enrichment was used to analyze the biological effects and functions of differential genes.Combined with the survival data of patients,the COX regression analysis was used to screen out the genes related to the patient′s prognosis,and then the risk score equation was constructed.The patients with colon cancer were divided into high-risk group and low-risk group according to risk scores.The sensitivity and specificity of the prognostic model were assessed by receiver operating characteristic curve.Results Compared with normal tissues,there were 72 dysregulated ferroptosis-related genes in colon cancer tissues.The differential genes were mainly involved in ferroptosis and tumor-related signaling pathways.Four ferroptosis-related genes(DRD4,TFAP2C,ENPP2,CAV1)were significantly related to the patient′s prognosis(P<0.05),which could be used for the construction of a risk prognosis model.The overall survival rate of patients in the high-risk group was poorer,and the difference was statistically significant(P<0.05).The areas under the curve of the molecular prognostic model based on ferroptosis-related genes for predicting the survival rates of patients at 1-year,3-year and 5-year were 0.714,0.750 and 0.759,respectively,which had good sensitivity and specificity.Conclusion A molecular prognostic model based on ferroptosis-related genes has been successfully constructed,which can better predict the prognosis of colon cancer patients.