锯齿状息肉病综合征的关键基因与潜在治疗药物的生物信息学筛选  

Bioinformatics screening of key genes and candidate therapeutic drugs of serrated polyposis syndrome

作　　者：任威瑞 张创 赵文娟[1] 张宇翔 王军民 REN Weirui;ZHANG Chuang;ZHAO Wenjuan;ZHANG Yuxiang;WANG Junmin(Department of Gastroenterology,the Third Hospital of Hebei Medical University,Shijiazhuang 050000;Department of Pediatric Surgery,the Second Hospital of Hebei Medical University,China)

机构地区：[1]河北医科大学第三医院消化内科,河北石家庄050000 [2]河北医科大学第二医院小儿外科

出　　处：《胃肠病学和肝病学杂志》2021年第4期418-423,共6页Chinese Journal of Gastroenterology and Hepatology

基　　金：河北省重点研发计划项目(19277729D)。

摘　　要：目的基于生物信息学方法利用GEO芯片数据库分析锯齿状息肉病综合征(serrated polyposis syndrome,SPS)的关键基因,探索SPS的分子调控机制及潜在的治疗药物。方法从GEO数据库下载GSE19963数据集,利用GEO2R分析SPS组织样本和正常结肠黏膜组织样本的表达数据,利用DAVID数据库对差异表达基因进行富集与功能注释。利用STRING数据库和Cytoscape软件构建蛋白质相互作用(protein-protein interaction,PPI)网络,分析其关键基因,利用药物基因组学数据库CMap探索具有潜在治疗SPS作用的小分子药物。结果从GSE19963芯片数据集中共获取230个差异表达基因,其中157个为上调基因,73个为下调基因。上调的差异表达基因显著富集于细胞间粘附、脂类物质的生物合成、氧化还原及类固醇的生物合成等过程,下调的差异表达基因显著富集于金属离子的结合、矿物质吸收及细胞色素P450途径等过程。根据PPI网络,筛选出5个关键基因。通过CMap数据库筛选到10个具有潜在治疗SPS作用的小分子药物。结论通过生物信息学筛选出的关键基因及构建的PPI网络有助于全面了解SPS发生的分子机制,为探索关键基因作为临床诊断及治疗的分子靶标提供了可靠的研究方向,筛选出的小分子药物可作为潜在治疗SPS作用的关键药物进行研发。Objective To identify the key genes associated with serrated polyposis syndrome(SPS)based on GEO databases,and explore the molecular mechanism of SPS and identify potential drug targets and candidate agents for SPS treatment.Methods Gene expression profiles of GSE19963 was available from GEO database.The differentially expressed genes(DEGs)was identified,and function enrichment analyses was performed.The protein-protein interaction(PPI)network was constructed and the module analysis was performed using STRING and Cytoscape software.Finally,small molecule drugs with potential treatment for SPS were analyzed by Connectivity Map(CMap)database.Results A total of 230 DEGs including 157 up-regulated and 73 down-regulated genes were identified.Functional annotations of the common DEGs indicated that up-regulated genes were significantly enriched for cell-cell adhesion,triglyceride biosynthetic process,oxidation-reduction process and cholesterol biosynthetic process;down-regulated genes were significantly enriched for cellular response to metal ion,perinuclear region of cytoplasm,carbonate dehydratase activity and drug metabolism-cytochrome P450.Five DEGs were screened by constructing a PPI network and module analysis.Some potential small molecular drugs for the treatment of SPS had also been screened.Conclusion DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the mechanism of SPS,and provide candidate targets for diagnosis and treatment of SPS,and the selected small molecular drugs can be developed as the key drugs for the treatment of SPS.

关 键 词：锯齿状息肉病综合征 生物信息学 差异表达基因 

分 类 号：R574[医药卫生—消化系统]