摘要
目的通过生物信息学分析为胰腺导管腺癌的研究提供潜在的生物标记物和治疗靶点。方法选择来自Gene Expression Omnibus(GEO)数据库的GSE15471、GSE62165、GSE28735的基因表达谱作为研究对象,用GEO2R筛选差异表达的基因(DEGs)。使用DAVID在线数据库对差异表达基因进行基因本体论(GO)和KEGG富集分析。通过STRING数据库构建了DEGs的PPI网络,并利用Cytoscape分析PPI网络中基因的连接度,从而筛选核心基因。用KM-plotter在线软件进一步对核心基因进行生存分析。结果共鉴定出170个上调的DEGs,54个下调的DEGs。通过富集分析发现,DEGs主要富集于胶原分解代谢过程、细胞外基质分解、蛋白水解、ECM-受体相互作用、黏着力、蛋白质消化吸收等通路。基于PPI网络中基因的连接度鉴定出十二个核心基因(COL1A1、COL3A1、COL5A2、COL6A3、FN1、ITGA2、MMP1、MMP9、TOP2A、ALB、EGF、POSTN)。进一步生存分析发现MMP1、MMP9、ITGA2、TOP2A、POSTN的高表达与胰腺导管腺癌患者不良预后有关。结论本研究通过生物信息学分析发现与胰腺导管腺癌发生发展相关的十二个核心基因,为胰腺导管腺癌的研究提供了潜在的生物标记物和治疗靶点。
Objective To provide potential biomarkers and therapeutic targets for the study of pancreatic ductal adenocarcinoma(PDAC)by bioinformatics analysis.Methods Gene expression profiles of GSE15471,GSE62165,and GSE28735 from the Gene Expression Omnibus(GEO)database were selected as subjects,and differentially expressed genes(DEGs)were screened using GEO2 R.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed on differentially expressed genes using the DAVID online database.Proteinprotein Interaction(PPI)network of DEGs was constructed by using STRING database,and the connectivity of genes in PPI network was analyzed by using Cytoscape to screen hub genes.KM-plotter online software was used for further survival analysis of hub genes.Results A total of 170 up-regulated DEGs and 54 down-regulated DEGs were identified in combination with three data sets.DEGs are mainly enriched in pathways such as collagen catabolism,extracellular matrix decomposition,proteolysis,ECM-receptor interaction,adhesion,protein digestion and absorption by enrichment analysis.Twelve hub genes(COL1 A1,COL3 A1,COL5 A2,COL6 A3,FN1,ITGA2,MMP1,MMP9,TOP2 A,ALB,EGF,POSTN)were identified based on the connectivity of genes in PPI network.Survival analysis showed that the high expression of MMP1、MMP9、ITGA2、TOP2 A、POSTN was found to be associated with poor prognosis in patients with pancreatic ductal adenocarcinoma.Conclusion 12 hub genes related to the occurrence and development of pancreatic ductal adenocarcinoma were found,which would provide potential biomarkers and therapeutic targets for the study of pancreatic ductal adenocarcinoma.
作者
李孟畔
沙磊
LI Meng-pan;SHA Lei(Department of Neuroendocrine Pharmacology,College of Pharmacy,China Medical University,Shenyang 110122,China)
出处
《解剖科学进展》
2020年第5期540-543,549,共5页
Progress of Anatomical Sciences
基金
国家自然科学基金(81270900)。
关键词
胰腺导管腺癌
基因芯片
生物信息学分析
Pancreatic ductal adenocarcinoma
gene chip
bioinformatics analysis
