膀胱尿路上皮癌预后相关甲基化相关基因的筛选与预后模型构建  

Screening of methylation-related genes and construction of prognostic model in bladder urothelial carcinoma

作　　者：路惠茹[1] 耿辉[2] 梁亮 张倩[1] 李磊[1] 殷锋彦[3] 罗晓辉[3] 吕军 李涛[3] LU Huiru;GENG Hui;LIANG Liang;ZHANG Qian;LI Lei;YIN Fengyan;LUO Xiaohui;LYU Jun;LI Tao(Department of Urology,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Physical Examination Center,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Department of Urology,Baoji Central Hospital,Baoji 721008,Shaanxi Province,China;Department of Clinical Research,The First Affiliated Hospital of Jinan University,Guangzhou 510630,China)

机构地区：[1]西安交通大学第一附属医院泌尿外科,西安710061 [2]西安交通大学第一附属医院健康医学科,西安710061 [3]宝鸡市中心医院泌尿外科,陕西宝鸡721008 [4]暨南大学附属第一医院临床研究部,广州510630

出　　处：《医学新知》2025年第3期319-327,共9页New Medicine

基　　金：陕西省社会发展领域一般项目(2024SF-YBXM-097)。

摘　　要：目的筛选膀胱尿路上皮癌(bladder urothelial carcinoma,BLCA)预后相关甲基化相关基因,并探讨其在BLCA预后中的价值。方法从TCGA数据库下载BLCA项目的样本数据,GeneCards数据库获取相关评分大于5的甲基化相关基因。使用Lasso回归筛选确定预后相关基因。GO及KEGG富集分析用于探索预后基因的功能和参与通路,Cox回归分析确定具有潜在预后价值的基因,采用受试者工作特征(ROC)曲线及曲线下面积(AUC)对预后模型进行评估。结果共获得411例带有临床样本的数据和206个甲基化相关基因。Lasso回归筛选出11种(VHL、THBS1、SMYD2、RARB、PRMT6、MYC、IGF2、ICMT、EGFR、DLEC1、CARM1)具有显著预后价值的甲基化相关基因。富集分析显示,其主要参与补体与凝血级联、神经活性配体-受体相互作用和酪氨酸代谢通路。多因素Cox回归分析结果表明,肿瘤浸润[HR=2.556,95%CI(1.190,5.491)]及IGF2高表达[HR=3.088,95%CI(1.348,7.075)]与BLCA预后不良相关,VHL高表达[HR=0.358,95%CI(0.151,0.845)]与BLCA预后改善相关,ROC分析显示,1年、3年和5年总生存期AUC值分别为0.773、0.719和0.725,表明预后模型预测性能较好。结论本研究筛选了11种有显著预后价值的甲基化相关基因,肿瘤浸润、IGF2高表达、VHL高表达可能与BLCA预后相关。Objective To screen for prognostic methylation-related genes in bladder urothelial carcinoma(BLCA)and explore their value in the prognosis of BLCA.Methods Download the sample data of the BLCA project from the TCGA database,obtain the methylation-related genes with a correlation score greater than 5 from the GeneCards database.Prognostic genes were identified using Lasso regression screening.GO and KEGG enrichment analysis were used to explore the functions and pathways involved in prognostic genes,and Cox regression analysis was used to identify genes with potential prognostic value.Receiver operator characteristic(ROC)curve and the area under the curve(AUC)was used to evaluate the prognostic model.Results A total of 411 data with clinical samples and 206 methylation-related genes were obtained.11 methylation-related genes with significant prognostic value were screened out,including VHL,THBS1,SMYD2,RARB,PRMT6,MYC,IGF2,ICMT,EGFR,DLEC1 and CARM1.Enrichment analysis showed that these genes were mainly involved in pathways such as complement and coagulation cascades,neuroactive ligand-receptor interactions,and tyrosine metabolism pathways.The results of the multivariate Cox regression analysis indicate that tumor invasion[HR=2.556,95%CI(1.190,5.491)]and high IGF2 expression[HR=3.088,95%CI(1.348,7.075)]were associated with poor prognosis in BLCA,whereas high VHL expression[HR=0.358,95%CI(0.151,0.845)]was a protective factor for BLCA.The ROC analysis showed that the AUC for overall survival at 1,3,and 5 years were 0.733,0.719,and 0.725 respectively,indicating that the prognostic model had good predictive performance.Conclusion This study identified 11 methylation-related genes,tumour infiltration,high IGF2 expression,and high VHL expression may be associated with BLCA prognosis.

关 键 词：膀胱尿路上皮癌 甲基化相关基因 TCGA GeneCards 预后 

分 类 号：R737.14[医药卫生—肿瘤]