基于生物信息学分析对儿童克罗恩病核心发病基因预测及诊治意义

Core genes prediction of pediatric Crohn′s disease based on bioinformatics analysis and its significance of diagnosis and treatment

目的应用生物信息学方法筛选出儿童克罗恩病(PCD)的差异基因(DEGs),探讨PCD的致病机制,为PCD的诊疗提供潜在靶点。方法从基因表达数据库(GEO)中获得健康对照和PCD患儿结肠组织的芯片数据库GSE126124,通过基因分析表达工具(GEO2R)筛选出DEGs。然后利用DAVID数据库对PCD的DEGs进行基因本体(GO)分析及京都基因和基因组百科全书(KEGG)分析。应用STRING数据库构建蛋白质相互作用网络(PPI),并通过Cytoscape3.9.1软件识别出前24个核心基因。最后在GSE3365基因芯片数据库中对核心基因进行表达量验证。结果从GSE126124芯片数据库中发现共有141个DEGs,其中39个上调,102个下调。这些DEGs参与免疫调节、肠道适应性改变、肠道黏膜屏障功能变化等多种细胞活动和机体调节。PPI共筛选出24个潜在核心基因,在验证数据库中均有明显的表达差异,其中兔CXC趋化因子配体2(CXCL2)、白细胞介素(IL)-1β差异最为显著。结论核心基因如CXCL2、IL-1β等很可能是PCD致病的关键基因,可能会成为PCD诊治的潜在靶点。

Objective To screen out differential expressed genes(DEGs)of pediatric Crohn′s disease(PCD)by bioinformatics method,and to explore the pathogenesis of PCD,so as to provide a potential target for the diagnosis and treatment of PCD.Methods The microarray database GSE126124 of colon tissue of healthy controls and children with PCD was obtained from the gene expression omnibus data base(GEO)and DEGs was screened by the gene expression omnibus data base to R(GEO 2R).Then,using the DAVID database,the DEGs of PCD was analyzed by the gene ontology(GO)and the Kyoto encyclopedia of genes and genomes(KEGG).The protein-protein interaction(PPI)was constructed using STRING database,and the first 24 core genes were identified by Cytoscape 3.9.1 software.Finally,the expression level of core genes was verified in GSE3365 gene chip database.Results A total of 141 DEGs were found in GSE126124 chip database,of which 39 were up-regulated and 102 were down-regulated.These DEGs were involved in immune regulation,intestinal adaptation,intestinal mucosal barrier function and other cellular activities and body regulation.A total of 24 potential core genes were screened from the PPI,and the expression differences were all significant in the validation databases,among which CXCL2 and IL-1βwere the most significant.Conclusion Core genes such as CXCL2 and IL-1βare likely to be the the key genes of PCD,and may become potential targets for diagnosis and treatment of PCD.