基于加权基因共表达网络的膀胱尿路上皮癌预后及疗效相关基因筛选  

Screening of genes related to prognosis and therapeutic effect in bladder urothelialcarcinoma based on weighted gene co-expression network analysis

作　　者：李佳丽 曾梓航 刘嘉彬 张冉 李硕 孟详喻 李胜[2,3] 李伟 LI Jiali;ZENG Zihang;LIU Jiabin;ZHANG Ran;LI Shuo;MENG Xiangyu;LI Sheng;LI Wei(Second Clinical Institution of Wuhan University,Wuhan Hubei 430071,China;Department of Urology,Zhongnan Hospital of Wuhan University,Wuhan Hubei 430071,China;Human Genetics ResourcePreservation Center of Hubei Province,Wuhan Hubei 430071,China;Department of oncology,the first people′s Hospital of Tianmen City,Tianmen Hubei 431700,China)

机构地区：[1]武汉大学第二临床学院,湖北武汉430071 [2]武汉大学中南医院泌尿外科 [3]湖北省人类遗传资源保藏中心 [4]湖北天门市第一人民医院肿瘤科,湖北天门431700

出　　处：《转化医学杂志》2020年第6期340-344,共5页Translational Medicine Journal

基　　金：湖北省卫生计生科研基金(WJ2019H211)。

摘　　要：目的构建加权基因共表达网络分析(weighed gene co-expression network analysis,WGCNA),鉴定出膀胱尿路上皮癌(bladder urothelial carcinoma,BLCA)中与预后及治疗效果相关的基因,并分析其在肿瘤相关通路中的活性。方法在癌症基因组图谱数据库获取膀胱尿路上皮癌的转录组测序及相应临床数据;选择年龄、性别、身高、体重、人种、生存时间、吸烟年数、治疗效果、病理分级、TNM分期及淋巴结浸润为临床表型进行加权基因共表达网络分析;利用R语言进行生存分析;利用GSCALite工具进行肿瘤相关的通路活性分析;利用基因表达汇编数据库中的GSE13507和GSE3167数据集进行验证。结果本研究鉴定出与预后及治疗效果均显著相关的基因模块及模块关键基因GPHN、CPSF2、PRMT5、EIF2S1、KLC1、SLC39A9、SRP54及CNIH,上述8个基因在肿瘤相关通路中有一定活性。结论GPHN、CPSF2、PRMT5、EIF2S1、KLC1、SLC39A9、SRP54及CNIH基因在BLCA中与预后及治疗效果均显著相关,并且参与了肿瘤相关通路,可能成为BLCA的生物标志物或潜在治疗靶点。Objective This study aimed to identify genes related to prognosis and therapy outcome in bladder urothelial carcinoma(BLCA)by Weighed Gene Co-expression Network Analysis(WGCNA)and analyze activity of these genes in the tumor related pathway.Methods Clinical and mRNA-seq data of BLCA were acquired from The Cancer Genome Atlas(TCGA).Clinical phenotypes were selected to performed WGCNA including age,gender,height,weight,race,days to death,tobacco smoking history,outcome,TNM,lymphovascular invasion and pathologic stage.Survival analysis was performed via R Language.Analysis of tumor related pathway activity was performed via GSCAL ite tool.GSE3167 and GSE13507 from Gene Expression Omnibus(GEO)database were used to validate.Results We identified WGCNA module significantly associated with prognosis and therapy outcome,even the module′s key genes included GPHN,CPSF2,PRMT5,EIF2S1,KLC1,SLC39A9,SRP54 and CNIH.These eight genes had certain activity in tumor related pathways.Conclusion GPHN,CPSF2,PRMT5,EIF2S1,KLC1,SLC39A9,SRP54 and CNIH were significantly related to the prognosis and treatment outcome in BLCA.These genes were involved in tumor related pathways,and may become biomarkers or potential therapeutic targets of BLCA.

关 键 词：膀胱尿路上皮癌 生物信息学 加权基因共表达网络 生物标志物 

分 类 号：R737.14[医药卫生—肿瘤]