首页|肾透明细胞癌甲基化驱动基因的筛选及其预后作用

肾透明细胞癌甲基化驱动基因的筛选及其预后作用

扫码查看
目的 筛选肾透明细胞癌甲基化驱动基因,并基于肾透明细胞癌甲基化驱动基因构建预后分子标签,探索其在肾透明细胞中的预后作用.方法 下载TCGA数据库中肾透明细胞癌基因的表达数据、DNA甲基化数据及临床信息资料.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,筛选甲基化驱动基因,然后随机抽取70%肾透明细胞癌患者的转录组数据,应用LASSO-Cox回归分析构建预后分子标签,取其余30%的数据验证构建分子标签.结果 根据肾透明细胞癌表达谱数据和甲基化数据,筛选得到188种肾透明细胞癌甲基化驱动基因(Cor<-0.3,均P<0.05),其中104种低甲基化驱动基因,84种高甲基化驱动基因;基于ccRCC转录组数据和生存数据,发现188种甲基化驱动基因中有91种与ccRCC预后相关的基因(均P<0.05).联合临床预后数据采用LASSO-Cox回归分析从中筛选出8种与肾透明细胞癌预后相关甲基化驱动基因EPB41L4B、GOLGA6L2、HHLA2、HOXA2、LINC00944、SPINT2、ZNF382、ZNF888,并联合8种甲基化驱动基因构建预后分子标签:分子标签得分=0.130004056 × EXPEPB41L4B+0.110026099 × EXPGOLGA6L2-0.116610796 × EXPHHLA2+0.438033838 × EXPHOXA2+0.180898961 × EXPLINC00944-0.168803405 × EXPSPINT2-0.326061874 × EXPZNF3821-0.152001589 × EXPZNF888.生存曲线分析结果显示,构建的分子标签值在训练组、测试组、全部数据组与ccRCC患者的生存期均显著相关(均P<0.05),分子标签值越高患者预后越差.结论 通过对TCGA数据库的挖掘,筛选得到188种肾透明细胞癌甲基化驱动基因,从中筛选出由8种基因联合组成的预后分子标签与肾透细胞癌患者的预后有显著性关联,为肾透细胞癌精准治疗提供了新的预后模型.
Screening of methylation driving genes in renal clear cell carcinoma and its prognostic role
Objective To screen methylation driving genes of renal clear cell carcinoma,con-struct prognostic molecular label based on methylation driving genes of renal clear cell carcinoma,and explore its prognostic role in renal clear cells.Methods The gene expression data,DNA methylation data and clinical information of renal clear cell carcinoma in TCGA database were downloaded.The MethylMix package of the R language was used to comprehensively analyze the patient's gene expres-sion data and DNA methylation data to screen methylation driving genes,and then the transcriptome data of 70%patients with renal clear cell carcinoma were randomly selected.The prognostic molecular tags were constructed by LASSO-Cox regression,and the constructed molecular tags were verified by 30%data.Results According to the expression profile data and methylation data of renal clear cell carcinoma,188 methylation driving genes were screened(Cor<-0.3,all P<0.05),104 were hypomethylation driving genes and 84 hypermethylation driving genes;Based on ccrcc transcriptome data and survival data,91 of the 188 methylation driving genes were found to be related to the progno-sis of ccrcc(P<0.05).Combined with the clinical prognosis data,eight methylation driver genes EPB41L4B,GOLGA6L2,HHLA2,HOXA2,LINC00944,SPINT2,ZNF382 and ZNF888 related to the prognosis of renal clear cell carcinoma were screened by lasso Cox regression analysis.The prognostic molecular tag was constructed by combining eight methylation driver genes:Risk score=0.130004056 × EXPEPB41L4B+0.110026099 × EXPGOLGA6L2-0.116610796 × EXPHHLA2+0.438033838 × EX-PHOXA2+0.180898961 × EXPLINC00944-0.168803405 × EXPSPINT2-0.326061874 × EX-PZNF3821-0.152001589 × EXPZNF888.Survival curve analysis results showed that the constructed molecular tag value was significantly correlated with the survival of ccRCC patients in the training group,the test group and all data groups(all P<0.05),and the higher the molecular tag value,the worse the prognosis of patients.Conclusions By mining of TCGA database,188 methylation driving genes of renal clear cell carcinoma were screened,of which 91 methylation driving genes were related to the prognosis of ccRCC,and a prognostic molecular tag composed of 8 genes is screened from 91 genes related to the prognosis of renal clear cell carcinoma,the constructed prognostic molecular tag has a significant correlation with the prognosis of patients with renal cell carcinoma,which provides a new prognostic model for the precise treatment of renal cell carcinoma.

DNA MethylationMethylation-Driven GenesClear Cell Carcinoma of Kidney

管波、张挺、单卫民

展开 >

安徽省阜阳市人民医院泌尿外科,阜阳 236000

安徽省阜阳市人民医院病理科,阜阳 236000

DNA甲基化 甲基化驱动基因 肾透明细胞癌

2021年度阜阳市卫生健康委科研立项课题

FY2021-003

2024

国际泌尿系统杂志
中华医学会,湖南省医学会

国际泌尿系统杂志

CSTPCD
影响因子:0.414
ISSN:1673-4416
年,卷(期):2024.44(1)
  • 16