膀胱癌关键基因的筛选及预后相关性分析  

Screening of key genes and correlation analysis of prognosis in bladder cancer

作　　者：高鑫 张淑芳[1] Gao Xin;Zhang Shufang(Central Laboratory,Affiliated Haikou Hospital of Xiangya Medical College,Central South University,Haikou,Hainan 570208,China;Chinese Academy of Medical Sciences&Peking Union Medical College,Tsinghua University,Beijing 100005,China;Clinical Laboratory,the fourth affiliated Hospital of Jishou University,The First People’s Hospital of Huaihua,Huaihua,Hunan 418000,China)

机构地区：[1]中南大学湘雅医学院附属海口医院中心实验室,海南海口570208 [2]中国医学科学院北京协和医学院(清华大学医学部)研究生院,北京100005 [3]吉首大学附属第四医院怀化市第一人民医院检验科,湖南怀化418000

出　　处：《感染．炎症．修复》2022年第3期131-137,共7页Infection Inflammation Repair

基　　金：国家自然科学基金资助项目(82160531);湖南省自然科学基金资助项目(2021JJ40427);吉首大学科研项目(Jdlc2021)。

摘　　要：目的:利用生物信息学方法筛选膀胱癌进展过程中相关差异基因并揭示其对膀胱癌预后影响的潜在分子机制。方法:从GEO数据库中下载膀胱癌芯片表达谱数据集GSE37815和GSE65635,通过生物信息学方法进行二次挖掘分析。结果:从两个数据集中共获得387个共同差异基因(djust P<0.05且|log_(2)FC|>1,FC为变化倍数),GO富集分析显示基因主要富集在调节细胞增殖、质膜、细胞骨架蛋白结合。KEGG通路富集主要涉及的通路有黏着斑通路、血管平滑肌收缩、紧密连接、细胞周期和补体-凝血级联。通过构建蛋白互作网络筛选出血管内皮生长因子A(VEGFA)、拓扑异构酶IIα(TOP2A)、细胞周期蛋白B1(CCNB1)和α-平滑肌肌动蛋白(ACTA2)4个关键基因。预后分析发现,其中两个基因ACTA2、VEGFA的表达与膀胱癌患者的预后相关(P<0.05)。结论:本研究通过生物信息学深入挖掘GEO数据库膀胱癌表达谱芯片数据集,筛选出5条膀胱癌进展相关通路和4个关键基因,有助于对膀胱癌发生和发展机制的理解,并为寻找膀胱癌治疗靶点和药物的开发提供了理论依据和参考。Objective:To identify differentially expressed genes associated with the progression of bladder cancer by bioinformatics and reveal their potential molecular mechanisms.Methods:The bladder cancer chip expression profile data GSE37815 and GSE65635 were downloaded from the GEO database,and re-analyzed by bioinformatics method.Results:A total of 387 common differential genes(djust P<0.05 and|log_(2) fold change(FC)|>1)were obtained from the two datasets.GO enrichment analysis showed that the genes were mainly enriched in regulation of cell proliferation,plasma membrane,and cytoskeletal protein binding.The TOP5 pathways involved in KEGG pathway enrichment are Focal adhesion,Vascular smooth muscle contraction,Tight junction,Cell cycle and Complement and coagulation cascades.4 key genes identified by constructing a PPI network were vascular endothelial growth factor A(VEGFA),topoisomerase IIα(TOP2A),cell cycle protein B1(CCNB1)andα-smooth muscle actin(ACTA2).Prognostic analysis found that the expression of two genes,ACTA2 and VEGFA,was associated with prognosis in patients with bladder cancer(P<0.05).Conclusions:This study identified five pathways and four key genes related to the progression of bladder cancer,which deepened understanding of the pathogenesis and development mechanism of bladder cancer,and provided important theoretical basis and reference for the search for therapeutic targets and drug development of bladder cancer.

关 键 词：膀胱癌 GEO数据库 生物信息学 基因 数据挖掘 

分 类 号：R737.14[医药卫生—肿瘤]