基于数据挖掘分析食管鳞癌相关核心基因

Analysis of hub genes related to esophageal squamous cell carcinoma based on data mining

目的利用生物信息学方法分析食管鳞癌基因表达谱芯片,筛选与食管鳞癌相关的核心基因,为食管鳞癌的分子诊断和精准靶向治疗奠定基础。方法从基因表达数据库(Gene Expression Omnibus,GEO)中寻找3个不同的食管鳞癌基因表达谱芯片GSE45168、GSE38129、GSE70409,利用GEO2R筛选出食管鳞癌较正常癌旁组织具有显著表达差异的基因(differentially expressed genes,DEGs)。通过Draw Venn Diagram对3个基因表达谱芯片的差异基因取交集,利用基因功能注释数据库DAVID(Database for Annotation,Visualization and Integrated Discovery)6.8对差异表达基因进行基因本体(Gene Ontology,GO)功能注释和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,利用蛋白互作(protein protein interaction,PPI)检索工具STRING 11.0和Cytoscape等软件对3个数据集进行蛋白互作分析,筛选出枢纽基因(hub gene)。利用GEPIA数据库分析hub基因差异表达情况。结果食管鳞癌与正常癌旁组织相比,具有显著表达差异的基因共2529个(上调1164个,下调1365个),在3个基因表达谱芯片中均有显著表达差异的基因有191个(上调68个,下调123个)。GO分析显示,差异表达基因的功能主要集中在胶原蛋白分解代谢的过程、细胞外基质的组成与分解、细胞外泌体等;KEGG富集分析显示,差异表达基因的通路主要涉及细胞外基质受体相互作用、黏着斑、PI3K-AKT信号通路等;STRING-MCODE分析得到蛋白互作中的30个hub基因。其中KIF20A、ASPM、VCAN与食管鳞癌的相关性未见报道,且与癌旁正常组织相比,其在食管鳞癌组织中表达上调。结论食管鳞癌的发生、发展存在复杂的调控网络。通过生物信息学分析筛选出来的3个核心基因KIF20A、ASPM、VCAN可能成为食管鳞癌治疗的有效靶点。

Objective To analyze the gene expression profile chip of esophageal squamous cell carcinoma by bioinformatics method,screen the hub genes related to esophageal squamous cell carcinoma(ESCC)and provide a basis for molecular diagnosis and precise targeted therapy of the carcinoma.Methods Three gene expression profile chips of ESCC,GSE45168,GSE38129 and GSE70409,were searched from the Gene Expression Omnibus(GEO)database,while the differentially expressed genes(DEGs)of esophageal squamous cell carcinoma compared with the normal adjacent mucosa were screened by using GEO2R software.The intersection of DEGs of the three gene expression profile chips was taken by using Draw Venn Diagram software.DAVID(Database for Annotation,Visualization and Integrated Discovery)6.8 was used to perform the GO(Gene Ontology)function annotation and KEGG(Kyoto Encyclopedia of Genes and Genomes)enrichment analysis for DEGs.Hub genes were screened by using the software of protein interaction retrieval tools STRING 11.0 and Cytoscape,of which the differential expression was analyzed by using GEPIA database.Results There were 2529 DEGs(1164 were up-regulated while 1365 were down-regulated)in ESCC tissues compared with normal adjacent tissues.A total of 191 DEGs(68 were up-regulated while 123 were down-regulated)were screened from intersection of three gene expression profile chips.GO analysis showed that the functions of DEGs were mainly focused on the process of collagen catabolism,composition and decomposition of extracellular matrix,and cell exosomes.KEGG enrichment analysis showed that the pathways of DEGs were mainly involved in extracellular matrix receptor interaction,adhesion plaques and PI3K-AKT signaling pathway.Thirty hub genes in protein interaction were obtained by STRINGMCODE analysis.The roles of KIF20A,ASPM and VCAN in esophageal squamous cell carcinoma have not been reported.Morever,the expressions of the three genes were significantly higher in ESCC tissues than in adjacent normal tissues.Conclusion The occurrence and development of ESCC is a complex network of regulation.Three hub genes,KIF20A、ASPM and VCAN,may be the effective targets for ESCC treatment.