基于生物信息学分析的成人溃疡性结肠炎关键基因预测  

Prediction of key genes in adult ulcerative colitis based on bioinformatics analysis

作　　者：布娅·米然别克 贺欢[1] 王秋玲 李得阳 艾合买江·库尔班江[1] 高峰[1] Buya·MIRANBIEKE;HE Huan;WANG Qiu-ling;LI De yang;Aihemaijiang·KUERBANJIANG;GAO Feng(Department of Gastroenterology,the People's Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Clinical Research Center for Digestive Diseases,830001,Urumqi,China)

机构地区：[1]新疆维吾尔自治区人民医院消化内科&新疆消化系统疾病临床研究中心,新疆乌鲁木齐

出　　处：《临床消化病杂志》2024年第4期239-244,共6页Chinese Journal of Clinical Gastroenterology

摘　　要：[目的]通过生物信息学方法挖掘溃疡性结肠炎(ulcerative colititis,UC)致病关键基因。[方法]从公共基因芯片数据平台下载GSE53306和GSE38713基因芯片数据集,对UC活动期患者、UC静止期患者和健康志愿者进行分析筛选差异表达基因(differentially expressed genes,DEGs);其中GSE53306包含16例UC活动期、12例UC静止期和12例健康志愿者,而GSE38713包含15例UC活动期、8例UC静止期和13例健康志愿者。使用R软件limma包筛选DEGs,设定阈值为基因表达差异倍数(fold change,FC)对数(Log2 FC)的绝对值≥2且P<0.05。然后使用DAVID数据库对靶基因进行富集分析,进一步应用STRING数据库进行构建蛋白质相互作用网络(protein-protein interaction,PPI),应用Cytoscape对模块中的共表达关系进行可视化和筛选关键基因。最后,将筛选出的关键基因使用GSE3365和GSE9452数据集验证其在UC患者和健康志愿者外周血及肠黏膜上皮中的表达差异。[结果]筛选得到21个DEGs,富集分析的结果显示DGEs定位在细胞质和细胞骨架,分子功能主要与蛋白水解酶正负调节相关;p53和白细胞介素17调控的信号通路可能参与了疾病的发生、发展。通过PPI筛选出SPINK4、REG4、GUCA2B等若干与UC相关联的候选基因,发现SPINK4和REG4在UC患者外周血细胞相较于健康志愿者表达上调。[结论]生物信息学方法帮助筛选出若干与UC相关的DEGs,为进一步研究UC发病机制提供了方向。[Objective]To analyze and discover key genes in pathological mechanism of ulcerative colitis(UC)using bioinformatics.[Methods]We downloaded GSE53306 and GSE38713 datasets from the Gene Expression Omnibus(GEO)and screened differentially expressed genes(DEGs)in patients with active UC,quiescent UC and healthy volunteers.There,inGSE53306 contained 16 active UC,12 quiescent UC and 12 healthy volunteers while GSE38713 contained 15 active UC,8 quiescent UC and 13 healthy volunteers.We used the limma package of R software to screen the DEGs,setting thresholds as absolute values of the logarithm of difference between gene expression(fold change,FC)(Log2 FC)≥2 and P-value<0.05.Then we used the DAVID database for enrichment analysis of hubgenes and further applied the STRING database to construct the protein-protein interaction network(PPI)with visualization using Cytoscape.Finally,we used GSE3365 and GSE9452 to verify expression of hubgenes in samples of peripheral blood mononuclear cells(PMBCs)and Intestinal mucosal epithelium from UC patients and healthy volunteers.[Results]Screened a total of 21 DEGs and enrichment analysis showed that DGEs were localized in the cytoplasm and cytoskeleton with their molecular functions mainly associated with positive and negative regulation of protein hydrolases.Furthermore,signaling pathways regulated by p53 and interleukin 17 might be involved in UC development.Several hubgenes associated with UC,such as SPINK4,REG4 and GUCA2B,were screened by PPI and we also found that SPINK4 and REG4 were up-regulated in PMBCs of UC patients compared to healthy volunteers.[Conclusion]The bioinformatics is helpful to screen several DEGs associated with UC,providing further direction for research of the potential mechanism in UC.

关 键 词：结肠炎 溃疡性 生物信息学 差异表达基因 富集分析 蛋白质相关作用网络 

分 类 号：R574.62[医药卫生—消化系统]