溃疡性结肠炎及其恶性并发症的生物信息学分析和潜在治疗药物筛选

Bioinformatics analysis of ulcerative colitis and its malignant complications and screening of potential therapeutic drugs

目的·利用生物信息学分析探究溃疡性结肠炎(ulcerative colitis,UC)及其恶性并发症的致病相关基因及潜在的药物治疗靶点。方法·从GEO(Gene Expression Omnibus)数据库下载4个基因表达数据集(GSE13367、GSE9452和GSE36807为UC组,GSE37283为UCN组),采用联合分析筛选差异基因。结合后续的免疫分析及基因相关性分析得到与UC及其恶性并发症相关的关键基因,并利用LINCS L1000数据库筛选若干具有潜在治疗效果的小分子药物。结果·通过对UC组及UCN组数据集的2次差异基因分析分别筛选出86个和253个显著差异表达基因。针对UC组差异基因的蛋白质相互作用(protein-protein interaction,PPI)网络进行的评分分析显示网络的核心基因为CXCL8(C-X-C motif chemokine ligand 8)。KEGG(Kyoto Encyclopedia of Genes and Genomes)富集分析表明CXCL8主要参与了IL-17信号通路中对中性粒细胞的招募作用。基于LINCS L1000数据库的筛选结果共发现3种针对CXCL8的小分子药物--紫铆因、左旋西替利嗪、伪麻黄素。结论·分析得到的核心差异表达基因CXCL8可能会成为治疗UC及其恶性并发症的新药物靶点。筛选出的3种小分子药物可能对UC及其恶性并发症具有潜在的治疗效果。

Objective · To explore the pathogenic genes and potential drug therapeutic targets of ulcerative colitis and its malignant complications by a variety of bioinformatics analysis. Methods · Four expression profiling datasets(GSE13367, GSE9452 and GSE36807 as UC group, and GSE37283 as UCN group) downloaded from the Gene Expression Omnibus(GEO) database were jointly analyzed to identify the differential genes. Key genes related to ulcerative colitis and its malignant complications were obtained by subsequent immunoassay and gene correlation analysis, and a number of small molecule drugs with potential therapeutic effects were screened by LINCS L1000 database. Results · Eighty-six and 253 significant differentially expressed genes were identified respectively in the differential gene analysis of UC group and UCN group. The scoring analysis of the node genes in protein-protein interaction(PPI) network of UC group showed that the core gene of the network was CXCL8. KEGG(Kyoto Encyclopedia of Genes and Genomes) enrichment analysis indicated that CXCL8 mainly participated in the recruitment of neutrophils in IL-17 signaling pathway, and three small molecule drugs(butein, levocetirizine, pseudoephedrine) for CXCL8 were found based on the screening results of LINCS L1000 database. Conclusion · The core differentially expressed gene CXCL8 may be a new drug target for the treatment of ulcerative colitis and its malignant complications. The three screened small molecule drugs may have potential treatment effect on ulcerative colitis and its malignant complications.