摘要
目的整合生物信息学分析法鉴定出肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)发生发展的关键通路和具有诊断价值的潜在生物学标志物。方法从美国国立生物技术信息中心基因表达数据库(gene expression omnibus,GEO)数据库下载3个高质量的肝内胆管癌基因芯片数据集(GSE26566、GSE32879和GSE45001)和TCGA数据库的胆管癌的高通量测序数据集。在R软件内使用Limma程序包筛选出差异表达基因(differentially expressed genes,DEGs),采用Cluster Profiler程序包进行基因本体论和京都基因与基因组百科全书富集分析,采用基因相互作用数据库检索工具(search tool for the retrieval of interacting genes,STRING)对DEGs进行蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络分析,并通过Cytoscape软件作图。通过GEPIA工具进一步验证枢纽基因的转录表达情况。绘制受试者工作特征(receiver operating characteristic,ROC)曲线分析评估枢纽基因对胆管癌诊断价值。利用Diseasemeth 2.0工具评价枢纽基因的甲基化水平。结果本研究共筛选并验证了382个DEGs,包括90个上调基因和292个下调基因。上调基因主要显著富集在PI3K-Akt信号通路,而碳代谢途径是下调基因的明显富集通路。构建了289个节点的PPI网络。通过PPI网络分析鉴定出了6个枢纽基因:PRSS23、LGALS1、VCAN、COL5A1、ITGB1和EHHADH。ROC结果显示6个枢纽基因都可以区分肿瘤组织和非肿瘤组织。结论通过整合生物信息学分析鉴定了6个枢纽基因,这些差异基因可能是ICC早期诊断的潜在分子生物标志物。
Objective To identify the key pathways and potential biomarkers with diagnotic value for the development of intrahepatic cholangiocarcinoma(ICC)by integrating bioinformatics analysis.Methods We downloaded 3 high-quality datasets of ICC gene microarray(GSE26566,GSE32879 and GSE45001)from Gene Expression Omnibus(GEO)and the high-throughput sequencing data of cholangiocarcinoma(CCA)from the Cancer Genome Atlas(TCGA)database.Differentially expressed genes(DEGs)were screened using the Limma package in R software;Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed with Cluster Profiler package.Protein-protein interaction(PPI)network analysis of DEGs was subsequently carried out using the Search Tool for the Retrieval of Interacting Genes(STRING)database and subsequently visualized with Cytoscape.In addition,the transcriptional expression of hub genes was further verified by Gene Expression Profiling Interactive Analysis(GEPIA),and their diagnostic value was assessed by receiver operating characteristic(ROC)curve.Finally,the methylation level of the hub genes was determined using Diseasemeth 2.0.Results In total,382 DEGs were screened and validated,including 90 up-regulated and 292 down-regulated genes.The up-regulated genes were noticeably enriched in PI3 K-Akt signaling pathway,while the down-regulated in the carbon metabolism pathway.A PPI network was constructed with 289 nodes,and 6 hub genes were identified by PPI analysis:PRSS23,LGALS1,VCAN,COL5 A1,ITGB1 and EHHADH.ROC curve results showed that all the hub genes distinguished tumor tissues from non-tumorous tissues.Conclusion Six hub genes are identified by integrative bioinformatics analysis,which may be potential molecular biomarkers for early diagnosis of ICC.
作者
刘波
付婷婷
郭晓冬
何平
王洪林
LIU Bo;FU Tingting;GUO Xiaodong;HE Ping;WANG Honglin(Department of Hepatopancreatobiliary Surgery,the Third Affiliated Hospital of Chengdu Medical College(Chengdu Pidu District People's Hospital),Chengdu,Sichuan Province,611730;Department of Nosocomial Infection Control,the Third Affiliated Hospital of Chengdu Medical College(Chengdu Pidu District People's Hospital),Chengdu,Sichuan Province,611730;Department of Hepatobiliary Surgery,the First Affiliated Hospital of Chongqing Medical University,Chongqing,400016,China)
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2021年第10期915-922,共8页
Journal of Third Military Medical University
基金
四川省卫健委科研课题普及应用项目(18PJ568)。
关键词
胆管癌
生物信息学
生物标志物
GEO
TCGA
cholangiocarcinoma
bioinformatics
biomarker
Gene Expression Omnibus
Cancer Genome Atlas database
