利用TCGA数据库构建基于miRNA的结直肠癌列线图预后模型

Exploiting the TCGA database to establish a nomogram prognostic model of miRNAs associated with colorectal cancer

目的利用癌症基因组图谱(TCGA)数据库筛选与结直肠癌患者总生存期(OS)相关的miRNA,构建基于miRNA的列线图(Nomogram)预后模型,并评估该模型的预测能力。方法下载并整合TCGA数据库中结直肠癌miRNA测序数据及临床信息,按3∶1比例随机分为训练队列(training cohort)和验证队列(validation cohort)。应用单因素Cox回归、拉索(LASSO)回归及多因素Cox回归分析确定一组与结直肠癌预后相关的miRNA并建立结直肠癌的预后风险评分,结合风险评分和临床指标构建Nomogram模型,通过受试者工作特征曲线(ROC)、一致性指数(C-index)、校准曲线及决策曲线分析法(DCA)评估预测效能。结果498例结直肠癌患者纳入研究,差异分析得到291个miRNA,风险评分=(0.05634381×miR-548u表达量)+(0.03900542×miR-4665-5p表达量)-(0.10097599×miR-887-3p表达量)。结合风险评分、年龄及TNM分期构建Nomogram预后模型。验证队列中Nomogram预后模型、风险评分及TNM分期的AUC值分别为0.752,0.720和0.673,Nomogram预后模型在训练队列和验证队列一致性指数分别为0.743和0.761,校准曲线显示Nomogram对5年OS的预测值和实际值具有良好的一致性,DCA显示Nomogram预后模型临床获益与TNM分期系统比较更高。结论Nomogram预后模型具有良好的预测能力,有助于结直肠癌患者的临床决策及预后评估。

Objective This study aims to identify miRNAs associated with overall survival(OS)in colorectal cancer patients using The Cancer Genome Atlas(TCGA)database,develop a miRNA-based nomogram prognostic model,and assess the model's predictive capability.Methods miRNA sequencing data and clinical information of colorectal cancer patients were downloaded and integrated from the TCGA database.The data were randomly divided into a training cohort and a validation cohort in a 3:1 ratio.Univariate Cox regression,LASSO regression,and multivariate Cox regression analyses were employed to identify a set of miRNAs related to colorectal cancer prognosis and to establish a prognostic risk score for colorectal cancer.A nomogram model was then constructed by combining the risk score with clinical indicators.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curves,concordance index(C-index),calibration curves,and decision curve analysis(DCA).Results A total of 498 CRC patients were included in the study.Differential analysis identified 291 miRNAs.The risk score was calculated as follows:Risk Score=(0.05634381×miR-548u expression)+(0.03900542×miR-4665-5p expression)-(0.10097599×miR-887-3p expression).A nomogram prognostic model was constructed incorporating the risk score,age,and TNM stage.In the validation cohort,the AUC values of the nomogram prognostic model,risk score,and TNM stage were 0.752,0.720,and 0.673,respectively.The C-index of the nomogram prognostic model in the training and validation cohorts were 0.743 and 0.761,respectively.The calibration curve demonstrated good agreement between the nomogram's predicted and actual 5-year OS.DCA showed that the nomogram prognostic model offered greater clinical benefit compared to the TNM staging system.Conclusion The nomogram prognostic model demonstrates strong predictive ability and may aid in clinical decision-making and prognosis assessment for colorectal cancer patients.