摘要
[目的]基于生物信息学分析探寻类风湿关节炎(RA)和动脉粥样硬化(As)相互影响及作用的分子机制。[方法]从GEO数据库下载RA和As的基因表达谱,通过测试集发现RA和As之间的差异表达基因,通过富集分析探讨常见差异表达基因的生物学作用。利用Cytoscape软件构建差异表达基因蛋白质-蛋白质相互作用网络并筛选核心基因。TRRUST数据库揭示的转录调控关系预测转录因子。转录因子在测试集中验证,核心基因通过验证集和血液样本验证。[结果]本研究共鉴定出198个差异表达基因。差异表达基因功能富集分析主要在细胞因子调控的信号通路、白细胞迁移、白细胞正向调控以及细胞因子与细胞因子受体相互作用中。Cytoscape展示了差异表达基因和基因聚类模块,得到核心基因CCL5、CCR1、CCR2、CCR5、IRF8、ITGAM、ITGB2、LCP2、NCF2和PTPRC,验证集结果显示基因尚且可靠。通过TRRUST预测出可调控CCR1和IRF8的转录调控因子STAT1,且验证结果可靠。qPCR验证结果显示,As合并RA的患者CCR1和IRF8的表达水平显著高于健康者。[结论]CCR1和IRF8产生的调节作用很可能是RA合并As的核心因素。
Aim To investigate the molecular mechanism of interaction between rheumatoid arthritis(RA)and atherosclerosis(As)based on bioinformatics analysis.Methods The gene expression profiles of As and RA were downloaded from GEO database,differentially expressed genes between RA and As were identified through the test sets,the biological function of common differentially expressed genes was studied by enrichment analysis.Cytoscape software was used to construct the differentially expressed gene protein-protein interaction network and screen the hub genes.Transcriptional regulatory relationship revealed by the TRRUST database predicts transcription factors.Transcription factors were validated by test sets,and hub genes were validated by validation sets and blood samples.Results A total of 198 differentially expressed genes were identified.Functional enrichment analysis showed that differentially expressed genes were mainly concentrated in signaling pathways regulated by cytokines,leukocyte migration,positive regulation of leukocytes,and interaction between cytokines and cytokine receptors.Cytoscape demonstrated the differentially expressed genes and gene clustering modules,obtained the hub genes CCL5,CCR1,CCR2,CCR5,IRF8,ITGAM,ITGB2,LCP2,NCF2 and PTPRC,and the results of validation sets showed that the genes were reliable.qPCR results showed that the expression levels of CCR1 and IRF8 in patients with As combined with RA were significantly higher than those in healthy people.Conclusion The regulatory effect of CCR1 and IRF8 is likely to be the hub factor of RA merging with As.
作者
裴吉翔
周宏稷
安毅
PEI Jixiang;ZHOU Hongji;AN Yi(Department of Cardiology,Affiliated Hospital of Qingdao University,Qingdao,Shangdong 266000,China;Department of Cardiology,Fushun Central Hospital,Fushun,Liaoning 113000,China)
出处
《中国动脉硬化杂志》
CAS
2024年第3期194-202,共9页
Chinese Journal of Arteriosclerosis
基金
青岛市高血压病重点实验室科研基金项目(1016)
国家自然科学基金项目(81071246)。
