生物信息学及实验验证S100A8为溃疡性结肠炎的致炎基因  

Research on S100 A 8 as a potential inflammatory gene in ulcerative colitis based on bioinformatics and experimental verification

作　　者：杨强 赵旦娅 钦丹萍[3] YANG Qiang;ZHAO Danya;QIN Danping(Department of Gastroenterology,Hangzhou Dingqiao Hospital,Hangzhou 310021,China;The First School of Clinical Medicine of Zhejiang Chinese Medical University,Hangzhou 310053,China;Department of Gastroenterology,the First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310006,China)

机构地区：[1]杭州市丁桥医院消化内科,杭州310021 [2]浙江中医药大学第一临床医学院,杭州310053 [3]浙江中医药大学附属第一医院消化内科,杭州310006

出　　处：《中国免疫学杂志》2024年第11期2241-2246,2256,共7页Chinese Journal of Immunology

基　　金：国家自然科学基金(81973617)。

摘　　要：目的:寻找溃疡性结肠炎(UC)的致炎因子。方法:从GEO中纳入3组人类基因芯片数据集,R软件分析其中两组数据集中的差异表达基因(DEGs),结合研究前期UC大鼠基因芯片的前20个DEGs取交集后筛选UC的核心基因。在另一个人类芯片数据集中利用ROC曲线评估核心基因的敏感度和特异度,CIBERSORT分析核心基因与免疫细胞的关系,蛋白互作(PPI)网络图识别与核心基因共表达的蛋白并进行功能富集分析,将核心基因与治疗UC的抗炎中药进行分子对接,通过体外实验验证核心基因与炎症的相关性以及抗炎中药对核心基因的作用。结果:S100A8是UC的核心基因,具有高敏感度和特异度(AUC=0.953),S100A8与中性粒细胞、活化的肥大细胞和单核细胞等免疫炎症细胞呈正相关,PPI及功能富集分析发现S100A8与RAS信号通路、PI3K-AKT信号通路、mTOR信号通路等炎症通路相关,抗炎中药雷公藤红素、黄芩苷、小檗碱与S100A8均有较好的结合力,体外实验提示S100A8在炎症中发挥重要作用,雷公藤红素、黄芩苷、小檗碱均能降低S100A8表达。结论:S100A8可能是UC的致炎核心基因,有望成为新的治疗靶点。Objective:To screen inflammatory factors of ulcerative colitis(UC).Methods:Three sets of human GeneChip datasets were included from Gene Expression Omnibus(GEO).Differentially expressed genes(DEGs)from two of datasets were analyzed with R software,and intersection and combination of top 20 DEGs of UC rat GeneChip were screened to identify core genes of UC.ROC curve was used to evaluate sensitivity and specificity of core genes in another human microarray data set.CIBERSORT was used to analyze relationship between core genes and immune cells,proteins co-expressed with core gene were identified using protein-protein interaction(PPI)network diagram and analyzed for functional enrichment.Molecular docking of core genes with anti-inflamma-tory herbal medicines for treatment of UC was performed.Correlation between core genes and inflammation and effect of anti-inflamma-tory traditional Chinese medicine on core genes were verified by in vitro experiments.Results:S100A8 was screened out as core gene of UC with high sensitivity and specificity(AUC=0.953).S100A8 was positively correlated with immune inflammatory cells such as neutrophils,activated mast cells and monocytes.PPI and enrichment analysis revealed that S100A8 was related to inflammatory path-ways such as RAS signaling pathway,PI3K-AKT signaling pathway and mTOR signaling pathway.Anti-inflammatory Chinese medi-cines triptolide,baicalin and berberine had good binding force with S100A8.In vitro experiments suggest that S100A8 played an im-portant role in inflammation,triptolide,baicalin and berberine could reduce expression of S100A8.Conclusion:S100A8 may be an inflammatory core gene of UC,and it is expected to become a new therapeutic target.

关 键 词：溃疡性结肠炎 生物信息学分析 S100A8 炎症 分子对接 

分 类 号：R574.1[医药卫生—消化系统]