基于TCGA数据库构建雌激素受体阳性乳腺癌患者的预后风险模型  

Construction of a risk prognosis model for ER-positive breast cancer based on TCGA database

作　　者：杨燕 贺鑫 龚鹏举 宋文静 魏蕾[2] 张京伟[1] YANG Yan;HE Xin;GONG Pengju;SONG Wenjing;WEI Lei;ZHANG Jingwei(Dept.of Breast and Thyroid Surgery,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei,China;Dept.of Pathology and Pathophysiology,Wuhan University School of Basic Medical Sciences,Wuhan 430071,Hubei,China)

机构地区：[1]武汉大学中南医院甲状腺乳腺外科,湖北武汉430071 [2]武汉大学基础医学院病理与病理生理学教研室,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2022年第2期243-249,共7页Medical Journal of Wuhan University

摘　　要：目的:构建微小RNA(miRNA)表达的预测雌激素受体(ER)阳性乳腺癌患者预后的风险模型。方法:分析了TCGA数据库下载的ER阳性乳腺癌患者的miRNA表达数据和临床资料,筛选出与ER阳性乳腺癌特异性相关的miRNA并构建了miRNA-临床的预测ER阳性乳腺癌患者3年和5年生存率的预测模型。受试者工作曲线(ROC)和校准曲线用于评估列线图的预测能力和准确性。最后分析了miRNA在他莫昔芬治疗复发组与未复发组的表达情况。使用DAVID工具进行miRNA靶基因的GO功能富集和KEGG信号通路富集。结果:Lasso回归分析最终得到与预后相关的4个miRNA(miR-331、miR-615、miR-653、miR-887)并计算风险评分,风险评分可以有效地区分低风险患者和高风险患者。随后,我们构建了包含风险评分和临床特征的预后模型。曲线下面积(AUC)显示,该模型具有较好的预测能力和准确性(3年AUC=0.768,5年AUC=0.849)。GSE37405数据集中miRNA表达分析显示miR-331在他莫昔芬治疗复发组的表达明显高于他莫昔芬治疗未复发组(P=0.018)。GO功能富集分析和KEGG信号通路分析表明,miR-331的靶基因主要参与蛋白质结合、转录调控和mRNA监视途径。结论:我们构建了miRNA-临床的预后模型,该模型可有效预测ER阳性乳腺癌患者的3年和5年生存率,并有利于制定个体化治疗决策。Objective: To construct a risk prognosis model of patients with estrogen receptor(ER)-positive breast cancer based on expression of miRNA. Methods: We analyzed the miRNA expression data and the patient’s clinical data downloaded from the TCGA database, screened unique miRNAs of ER-positive breast cancer, and establish an miRNA-clinical prognostic model for predicting the 3-year and 5-year survival rate of patients with ER-positive breast cancer. Receiver operating characteristic curve(ROC) and calibration curve were used to evaluate the discriminative ability and accuracy of the nomogram. Finally, the expression of miRNAs in the relapsed group and the non-relapsed group after tamoxifen treatment was analyzed. GO function annotation and KEGG signaling pathways of the target genes of miRNA were performed using DAVID tools. Results: Though lasso regression analysis,four miRNAs related to prognosis(miR-331, miR-615, miR-653, and miR-887)were screened out and the risk score was calculated which could effectively distinguish low-risk patients from high-risk patients. Furthermore, we established a prognostic model incorporating the risk score and clinical characteristics. Area under curve(AUC) showed that the model had a good predictive ability and accuracy(AUC of 3-year=0. 768, AUC of 5-year=0. 849). The expression of miR-331 in the relapsed group after tamoxifen-treated was significantly higher than that in the non-relapsed group(P=0. 018).GO analysis and KEGG signaling pathway analysis showed that the target genes of miR-331 were mainly enriched in protein binding, transcriptional regulation and mRNA surveillance pathway.Conclusion: We established a miRNA-clinical prognostic model, which could effectively predict the 3-year and 5-year survival rate of patients with ER-positive breast cancer and has the helpful to make individualized treatment decisions.

关 键 词：雌激素受体阳性乳腺癌 miRNA TCGA 列线图 

分 类 号：R737.9[医药卫生—肿瘤]