基于甲基化驱动基因构建膀胱尿路上皮癌分子亚型和预后分子模型
Molecular subtypes and prognostic molecular models of bladder urothelial carcinoma based on methylation driv-en genes
张挺 1管波 2王浩宇 2单卫民 2王德彪3
作者信息
- 1. 236000 阜阳,安徽省阜阳市人民医院病理科
- 2. 236000 阜阳,安徽省阜阳市人民医院泌尿外科
- 3. 阜阳市肿瘤医院病理科
- 折叠
摘要
目的 筛选膀胱尿路上皮癌(BLCA)甲基化驱动基因,并基于其甲基化程度构建分子亚型和预后分子模型,探索其在BLCA中的预后作用.方法 在癌症基因组图谱(TCGA)数据库中下载BLCA转录组数据、DNA甲基化数据以及 BLCA患者的临床资料,使用 R语言 MethylMix包综合分析患者的基因表达数据和 DNA 甲基化数据并筛选甲基化驱动基因,利用 R 语言中 NMF 包对BLCA甲基化驱动基因表达进行无监督聚类分析,构建基于甲基化驱动基因的 BLCA分子亚型,探索不同亚型的预后情况和肿瘤微环境情况;采用LASSO-Cox回归分析筛选与BLCA预后相关的甲基化标志物,并构建预后分子模型,进一步探索其在BLCA中的预后作用.结果 根据BLCA表达谱数据和甲基化数据,筛选得到共 190 种 BLCA甲基化驱动基因;基于 BLCA转录组数据和生存数据,发现 190 种甲基化驱动基因中有 26 种与BLCA预后相关(P<0.05),基于这 26 种甲基化驱动基因的甲基化程度构建了BLCA分子亚型,不同亚型BLCA的预后不同,且不同亚型BLCA的肿瘤微环境也不同;基于 26 种甲基化驱动基因,采用LASSO-Cox回归分析从中筛选出 4 种与BLCA预后相关的甲基化驱动基因,分别为ARHGDIB、IDH2、LURAP1 和 PAXIP1-AS1,并联合这 4 种甲基化驱动基因构建了预后分子模型,其可以很好的判断BLCA患者的预后.结论 本研究通过对癌症基因组图谱数据库的挖掘,发现有 26 种甲基化驱动基因与BLCA预后相关,同时,构建了BLCA新的分子亚型和预后分子模型,不同亚型BLCA的预后和肿瘤微环境均不同,预后分子模型能够很好的预测BLCA患者的预后.
Abstract
Objective To screen methylation driven genes in bladder urothelial carcinoma(BLCA),construct molecular subtypes and prognostic molecular models based on their methylation levels,and ex-plore their prognostic role in BLCA.Methods BLCA transcriptome data,DNA methylation data and clinical data of patients with BLCA were downloaded from the Cancer Genome Atlas(TCGA)database.The gene expression data and DNA methylation data of patients were comprehensively analyzed using the R language MethylMix package,and methylation driven genes were screened.The expression of BLCA meth-ylation driven genes was unsupervised cluster analyzed using the NMF package in the R language,and the prognosis and tumor microenvironment of different subtypes were explored.LASSO Cox regression analy-sis was used to screen methylation markers related to the prognosis of BLCA,and a prognostic molecular model was constructed to further explore its prognostic role in BLCA.Results One hundred and ninety BLCA methylation driven genes were screened according to BLCA expression profile and methylation data;Based on BLCA transcriptome data and survival data,it was found that 26 of 190 methylation driven genes were related to the prognosis of BLCA(P<0.05).BLCA molecular subtypes were constructed based on the methylation degree of these 26 methylation driven genes.The prognosis of different subtypes of BLCA were different,and the tumor microenvironment of different subtypes of BLCA were also different;Based on twenty-six methylation driven genes,four methylation driver genes related to the prognosis of BLCA were screened out by LASSO-Cox regression analysis,namely ARHGDIB,IDH2,LURAP1 and PAXIP1-AS1.A prognostic molecular model was constructed by combining these four methylation driven genes,which can well judge the prognosis of BLCA patients.Conclusions Through the mining of TCGA Database,this study found that twenty-six methylation driven genes were related to the prognosis of BLCA.At the same time,a new molecular subtype and prognostic molecular model of BLCA were constructed.The prognosis and tumor microenvi-ronment of different subtypes of BLCA were different,and the prognostic molecular model could well predict the prognosis of BLCA patients.
关键词
膀胱尿路上皮癌/甲基化驱动基因/DNA甲基化/预后Key words
Bladder urothelial carcinoma/Methylation driven gene/DNA methylation/Prognosis引用本文复制引用
出版年
2024
NETL
NSTL
万方数据