基于生物信息学探讨支气管哮喘与溃疡性结肠炎“异病同治”机制

Exploring the mechanism of homotherapy for heteropathy between bronchial asthma and ulcerative colitis based on bioinformatics

目的:通过生物信息学分析确定支气管哮喘(哮喘)和溃疡性结肠炎(UC)共有的潜在生物标志物,并探讨这两种疾病的共同发病机制。方法:从GEO数据库下载包含529例哮喘患者、637例UC患者和147例健康对照者样本的数据集GSE76262、GSE206285、GSE69683和GSE87466,其中GSE76262和GSE206285用作训练数据集,GSE69683和GSE87466作为独立验证数据集。通过limmaR软件包筛选哮喘、UC患者和健康对照者样本的差异表达基因(DEGs),将两种疾病相关DEGs取交集得到哮喘和UC共同DEGs。构建蛋白质-蛋白质互作(PPI)网络,利用cytoHubba筛选出PPI网络的核心生物标志物,并对其进行功能注释、富集分析和表达验证。结果:共筛选出209个哮喘和UC共同DEGs,其中112个基因上调,97个基因下调。MMP9、CCL2、SELL、CCR7、ICAM1、ITGAX、NFKBIA、CXCR4、AGPS和TLR2被鉴定为哮喘和UC共同的核心生物标志物,RELA和NFKB1是关键转录因子。功能富集分析显示,核心DEGs主要参与趋化因子和细胞因子活性和脂质与动脉粥样硬化。结论:MMP9、CCL2、SELL、CCR7、ICAM1、ITGAX、NFKBIA、CXCR4、AGPS和TLR2是哮喘和UC的潜在核心基因;哮喘和UC共病机制可能涉及趋化因子和细胞因子活性、NF-κB信号通路以及脂质与动脉粥样硬化。

Objective:To identify the potential shared biomarkers between bronchial asthma(asthma)and ulcerative:colitis(UC)through bioinformatics analysis and explore their common pathogenic mechanism.Methods:The datasets GSE76262,GSE206285,GSE69683,and GSE87466 containing samples from 529 asthma patients,637 UC patients,and 147 healthy controls,were downloaded from GEO database.The datasets GSE76262 and GSE206285 were used as the training datasets,while GSE69683 and GSE87466 were used as independent validation datasets.The differentially expressed genes(DEGs)of the samples from asthma,UC patients and healthy controls were screened by limma R software package,and the common DEGs of asthma and UC were obtained by taking the intersection of the two disease related DEGs.A protein-protein interaction(PPI)network was constructed to identify key biomarkers shared between asthma and UC.The cytoHubba algorithm was used to select core biomarkers with high degree within the PPI network.Functional annotation,enrichment analysis,and expression validation were conducted to gain insights into the biological.functions of these biomarkers and their relevance to both diseases.Results:A total of 209 common DEGs were identified between asthma and UC,comprising 112 upregulated genes and 97 downregulated genes.MMP9,CCL2,SELL,CCR7,ICAM1,ITGAX,NFKBIA,CXCR4,AGPS,and TLR2 were identified as core biomarkers shared between asthma and UC.RELA and NFKB1 are key transcription factors in this context.Functional enrichment analysis showed that these DEGs were mainly involved in chemotactic and cytokine activities as well as lipid and atherosclerosis.Conclusion:The genes MMP9,CCL2,SELL,CCR7,ICAM1,ITGAX,NFKBLA,CXCR4,AGPS,and TLR2 represent potential core genes implicated in the pathogenesis of asthma and UC.The comorbid mechanisms of asthma and UC may involve chemokine and cytokine activities,NF xB signaling pathway,as well as lipid and atherosclerosis.