冠状动脉粥样硬化性心脏病患者心外膜脂肪组织和皮下脂肪组织之间差异表达基因的生物信息学分析

Differentially expressed genes between epicardial adipose tissue and subcutaneous adiposetissue in patients with coronary atherosclerotic disease:a bioinformatics analysis

目的利用生物信息学方法分析冠状动脉粥样硬化性心脏病(CAD)患者的心外膜脂肪组织(EAT)和皮下脂肪组织之间的差异表达基因,以探索CAD的发病机制。方法从GEO数据库中下载CAD患者EAT和皮下脂肪组织的转录组测序数据和表达矩阵,包括2个数据集(GSE24425、GSE64554)。应用edgeR算法筛选EAT和皮下脂肪组织之间的差异表达基因。针对差异表达基因进行基因本体论分析及京都基因与基因组百科全书信号通路分析,并构建蛋白-蛋白相互作用(PPI)网络图。利用Cytoscape3.1.2软件和MCODE插件进行可视化分析并筛选关键基因,并预测可以调控关键基因的微小RNA(miRNA)。结果取两个数据集的交集后共得到76个差异表达基因,包括上调基因41个,下调基因35个,其主要涉及嗜酸性粒细胞趋化性、细胞对脂质的反应、细胞外基质、胚胎骨骼系统发育、上皮管形态发生、上皮细胞分化等生物学过程,且主要富集在细胞因子-细胞因子受体相互作用、朊病毒病、精氨酸和脯氨酸代谢信号通路中。从PPI网络中共获取10个关键基因,包括CC基序趋化因子配体(CCL)2、CCL5、CCL8、CCL21、早期生长反应蛋白2(EGR2)、白细胞介素7受体(IL-7R)、同源异型盒(HOX)A5、HOXB5、HOXB7和HOXC8,其中hsa-miRNA-196a-5p和hsa-miRNA-196b-5p与HOXA5、HOXB7、HOXC8高度相关。结论CCL2、CCL5、CCL8、CCL21、EGR2、IL-7R、HOXA5、HOXB5、HOXB7和HOXC8在CAD患者EAT中表达失调,EAT可能通过促炎和免疫途径参与CAD的发生、发展。

Objective To apply the bioinformatics method to analyzing the differentially expressed genes between epicardial adipose tissue(EAT)and subcutaneous adipose tissue(SAT)in patients with coronary atherosclerotic disease(CAD),and to explore the pathogenesis of CAD.Methods Transcriptome sequencing data and expression array foREAT and SAT of CAD patients were downloaded from the GEO database,including two data sets(GSE24425 and GSE64554).The differentially expressed genes between EAT and SAT were screened using edgeRalgorithm.The Gene Ontology(GO)analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway analysis were conducted on the differentially expressed genes,and the protein-protein interaction(PPI)network was developed.Cytoscape3.1.2 software and MCODE plug-in were employed to perform the visualized analysis and identification of key genes,in addition,the microRNAs(miRNAs)which could modulate key genes were predicted.Results The intersection of the two data sets was done to obtain 76 differentially expressed genes,including 41 up-regulated genes and 35 down-regulated genes,which mainly involved eosinophil chemotaxis,cellulaRresponse to lipid,extracellulaRmatrix,embryonic skeletal system development,epithelial tube morphogenesis,epithelial cell differentiation and otheRbiological processes,and mainly enriched in cytokine-cytokine receptoRinteraction,prion disease,arginine and proline metabolism signaling pathway.Ten key genes were obtained from the PPI network,including C-C motif chemokine ligand(CCL)2,CCL5,CCL8,CCL21,early growth response protein 2(EGR2),interleukin 7 receptor(IL-7R),homeobox(HOX)A5,HOXB5,HOXB7 and HOXC8,wherein hsa-miRNA-196a-5p and hsa-miRNA-196b-5p highly correlated with HOXA5,HOXB7 and HOXC8.Conclusion Dysregulation in the expression of CCL2,CCL5,CCL8,CCL21,EGR2,IL-7R,HOXA5,HOXB5,HOXB7 and HOXC8 is observed in EAT of CAD patients.EAT may involve in the development and progression of CAD via a pro-inflammatory and immunological approach.