基于生物信息学分析ANCA相关性血管炎肾损害关键基因

Screening of Hub Genes of ANCA-associated Vasculitis with Renal Damage Based on Bioinformatics Analysis

目的通过生物信息学方法探究抗中性粒细胞胞质抗体(ANCA)相关性血管炎肾损害发生、发展的关键基因,寻找潜在的特异性分子标志物,为治疗ANCA相关性血管炎肾损害潜在靶标提供理论依据。方法从GEO数据库检索获得GSE108109和GSE108113芯片数据,利用R语言相关程序包处理、分析基因芯片GSE108109并筛选差异基因。利用Cytoscape软件中的MCODE插件筛选出关键基因,并利用GSE108113芯片数据对关键基因进行再次验证。结果筛选GSE108109芯片得到了187个差异基因,其中表达上调的基因35个,表达下调的基因152个。通过蛋白-蛋白相互作用网络模块化分析获得了9个核心基因,分别为CD53、C1QC、TYROBP、CSF1R、CYBB、LAPTM5、FCER1G、CTSS和C3AR1。通过GSE108113芯片数据对上述9个基因进行验证发现,CD53、C1QC、TYROBP、CSF1R、CYBB、LAPTM5、FCER1G和CTSS在ANCA相关性血管炎肾损害患者样本中表达显著上调,而C3AR1基因在ANCA相关性血管炎肾损害患者样本与健康成年人肾脏活组织样本间的表达并无显著差异。结论通过生物信息学分析获得8个核心基因在ANCA相关性血管炎肾损害的发生、发展中发挥重要作用,为探究ANCA相关性血管炎肾损害的发病机制、发现诊断标志物和探索靶向治疗新位点提供理论依据。

Objective To explore the hub genes of the occurrence and development of ANCA-related vasculitis with renal damage by bioinformatics,and to find the potential specific molecular markers,which provides a theoretical basis for the treatment of ANCA-related vasculitis with renal damage potential targets.Methods GSE108109 and GSE108113 microarrays data were retrieved from the GEO database,and the R software related package was used to process,analyze the microarrays GSE108109 and screen the differential genes.The hub genes were selected using the MCODE plug-in in the Cytoscape software,and the hub genes were re-verified by the data of GSE108113 microarrays.Results 187 differential genes were obtained by screening GSE108109 microarrays,among which 35 genes were up-regulated and 152 genes were down-regulated.9 hub genes,CD53,C1QC,TYROBP,CSF1R,CYBB,LAPTM5,FCER1G,CTSS and C3AR1,were identified by protein-protein interaction network modular analysis.The expression of CD53,C1QC,TYROBP,CSF1R,CYBB,LAPTM5,FCER1G and CTSS were significantly up-regulated in ANCA-related vasculitis with renal damage samples,but there was no significant difference between the expression of C3AR1 in ANCA-related vasculitis with renal damage samples of healthy adults.Conclusion Through bioinformatics analysis,eight core genes play an important role in the occurrence and development of ANCA-related vasculitis with renal damage,providing theoretical basis and new direction for exploring the pathogenesis of ANCA-related vasculitis with renal damage,finding diagnostic markers and exploring new targeted therapeutic sites.