摘要
目的:筛选膀胱癌(bladder cancer,BC)进展关键基因,探讨其生物学作用并为寻找潜在的治疗靶点提供依据。方法:从GEO数据库中检索获取BC患者的基因芯片数据,经R软件筛选肌层浸润性膀胱癌(muscular invasive bladder cancer,MIBC)与非肌层浸润性膀胱癌(non-muscle invasive bladder cancer,NMIBC)差异表达基因(differentially expressed genes,DEGs),并用clusterProfiler软件包进行DEGs功能注释、通路分析。利用STRING在线数据库联合Cytoscape软件进行蛋白互作(proteinprotein interaction,PPI)网络分析,筛选中枢基因。用GEPIA在线分析工具中的TCGA数据库进行预后分析,筛选关键基因。在Oncomine肿瘤数据库中验证关键基因表达水平,并导入SPSS 22.0软件进行统计学分析。再基于THE HUMAN PROTEIN ATLAS免疫组化结果,验证关键基因在不同侵袭性BC中的表达水平。结果:共筛选出DEGs 193个,其中表达上调116个,表达下调77个。这些基因主要涉及细胞外基质组织的生物过程、细胞组分构成、分子功能及MAPK信号通路。PPI分析获得65个中枢基因,预后分析得到6个关键基因的表达水平与BC患者总生存时间差异具有统计学意义(P<0.01)。Oncomine数据库验证表明CXCL12、ANXA5、ACTA2、TAGLN、COL6A2等5个关键基因在MIBC中明显上调,PPARG在MIBC中明显下调(P<0.05)。结论:细胞外基质的生物作用、MAPK通路及6个关键基因(CXCL12、ANXA5、ACTA2、TAGLN、COL6A2、PPARG)对肿瘤侵袭的改变可能成为抑制BC进展的潜在治疗靶点。
Objective:To screen key genes in the progression of bladder cancer(BC)and explore their biological effects,providing a basis for finding potential therapeutic targets.Methods:The data of BC patients were retrieved from the GEO database.Differentially expressed genes(DEGs)of muscular invasive bladder cancer(MIBC)and non-muscle invasive bladder cancer(NMIBC)were screened by R software;the cluster Profiler software package was used for DEGs function annotation and path analysis.The STRING online database combined with Cytoscape software was used to analyze protein-protein interaction(PPI)network and screen central genes and key templates.TCGA database of GEPIA online analysis tool was used for prognostic analysis and screening key genes.The expression level of key genes was validated in Oncomine Tumor Database and imported into SPSS 22.0 for statistical analysis.The expression level of key genes in different invasive BC were verified based on the immunohistochemical results of The HUMAN PROTEIN ATLAS.Results:A total of 193 DEGs were screened,among which 116 were up-regulated and 77 were down-regulated,which were mainly involved in the biological processes of extracellular matrix tissues,cellular component composition,molecular functions,and signaling pathways such as MAPK.A total of 65 central genes were obtained after PPI analysis,and the prognostic analysis of central genes showed that expression levels of six key genes were significantly correlated with the overall survival time of BC patients,with statistically significant differences(P<0.01).Oncomine database validation showed that five key genes of CXCL12,ANXA5,ACTA2,TAGLN and COL6 A2,were significantly up-regulated in MIBC,while PPARG was significantly down-regulated in MIBC(P<0.05).Conclusion:Changes of biological effects of extracellular matrix,MAPK pathway and six key genes(CXCL12,ANXA5,ACTA2,TAGLN,COL6 A2 and PPARG)on tumor invasion may become potential therapeutic targets to inhibit the progression of BC.
作者
李攀
曹金龙
姚志强
汉大黎
吴昊
张向向
陈朝虎
田俊强
Li Pan;Cao Jinlong;Yao Zhiqiang;Han Dali;Wu Hao;Zhang Xiangxiang;Chen Chaohu;Tian Junqiang(Department of Urology,Lanzhou University Second Hospital)
出处
《重庆医科大学学报》
CAS
CSCD
北大核心
2021年第1期57-64,共8页
Journal of Chongqing Medical University
基金
中央高校基本科研业务费专项资金资助项目(编号:561219007)
甘肃省卫生行业科研计划资助项目(编号:GSWSKY2017-10)
甘肃省兰州市城关区科技局科技攻关类资助项目(编号:2017KJGG0052)
兰州大学第二医院博士科研启动基金资助项目(编号:ynbskyjj2015-2-7)
兰州大学第二医院“萃英科技创新”计划资助项目(编号:CY2017-BJ16)
兰州大学第二医院萃英研究生指导教师培育计划资助项目(编号:201704)。
关键词
膀胱癌
生物信息学
基因芯片
差异表达基因
bladder cancer
bioinformatics
gene chip
differentially expressed gene
