摘要
目的筛选肾透明细胞癌进展相关基因。方法通过构建共表达网络筛选肾透明细胞癌进展相关基因并进行初步验证。结果基于GSE36895数据得到2 173个差异基因用于构建共表达网络。通过共表达网络确定与肾透明细胞癌进展最相关的棕色模块(r=0.52)为枢纽模块,进一步筛选得到6个枢纽基因TOP2A、CDK1、CDC20、KIF11、CCNB2、BUB1。通过测试集GSE73731数据对枢纽基因进行验证,各枢纽基因表达量与肾透明细胞癌进展均呈显著正相关(P<0.000 1);其中CDC20、BUB1对于低级别(gradeⅠ、Ⅱ)及高级别(gradeⅢ、Ⅳ)肾透明细胞癌有较高的诊断效能(AUC>0.7,P<0.000 1)。另外基于TCGA数据,各枢纽基因表达量与肾透明细胞癌病理分期及预后均显著相关。GO富集及KEGG通路分析显示枢纽模块基因显著富集于细胞周期相关生物过程及通路。GSEA显示枢纽基因高表达组主要富集于细胞周期及免疫相关通路。结论通过WGCNA构建共表达网络筛选得到的6个枢纽基因与肾透明细胞癌进展及预后密切相关,枢纽基因可能通过细胞周期相关通路来影响肾透明细胞癌进展及预后。
Objective To identify hub genes associated with the progression of clear cell renal cell carcinoma(ccRCC).Methods The hub genes associated with the progression of ccRCC were identified with weighted gene co-expression network analysis(WGCNA)and validated with bioinformatic analyses.Results A total of 2 173 differentially expressed genes were identified based on microarray data of GSE36895.The brown module(r=0.52)was identified as the hub module by constructing a gene co-expression network and then 6 hub genes(TOP2A,CDK1,CDC20,KIF11,CCNB2 and BUB1)were eventually identified.In the training set,all hub genes showed positive correlation with ccRCC progression(P<0.000 1);ROC curves indicated that CDC20 and BUB1 exhibited excellent diagnostic efficiency(AUC>0.7,P<0.000 1)for low-grade and high-grade ccRCC.In addition,all hub genes showed positive correlation with ccRCC pathologic stage and prognosis based on TCGA data.Functional enrichment analysis revealed that genes in hub module were significantly enriched in cell proliferation associated GO terms and cell cycle pathway.Besides,gene set enrichment analysis(GSEA)showed that gene sets associated with cell cycle related pathways were mainly enriched in the samples with hub genes highly expressed.Conclusion The 6 hub genes identified by WGCNA are closely associated with the progression and prognosis of ccRCC.Besides,these hub genes may influence the progression and prognosis of ccRCC by regulating the proliferation of tumor cells.
作者
石胜军
田斌群
SHI Sheng-jun;TIAN Bin-qun(Department of Urology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)
出处
《现代泌尿外科杂志》
CAS
2018年第12期910-916,共7页
Journal of Modern Urology
关键词
肾透明细胞癌
加权基因共表达网络分析
基因芯片
枢纽基因
clear cell renal cell carcinoma
weighted gene co-expression network analysis
microarray
hub gene
