糖尿病肾病特异性肾小管间质纤维化相关基因生物信息学分析

Bioinformatics analysis of diabetic nephropathy specific tubulointerstitial fibrosis related genes

目的通过生物信息学分析方法探讨糖尿病肾病(diabetic nephropathy,DN)肾小管间质纤维化(renal tubuleinterstitial fibrosis,RTF)的关键基因及其临床相关性。方法下载DN、非DN患者肾间质组织和RTF模型小鼠肾组织数据集,筛选差异表达基因,识别DN特异性RTF相关基因,并进行功能富集和蛋白质相互作用网络(protein-protein interaction,PPI)分析,筛选出关键基因后进行临床相关性分析。结果共获得125个DN特异性RTF相关基因。生物学功能富集分析提示上述基因与免疫反应及代谢过程相关,并富集到了Toll样受体、核因子-κB、肿瘤坏死因子和趋化因子等信号通路。基于PPI网络分析筛选了ITGAM、TLR2、LCP2、TLR7、IL10RA作为关键基因,在DN组表达差异倍数显著高于对照组,且受试者工作特曲线的曲线下面积分别为1、0.925、0.9583、0.9583、0.8833(P<0.01)。关键基因的表达水平与估算肾小球滤过率的Pearson相关系数(r值)分别为-0.7956、-0.6463、-0.752、-0.7136、-0.7721(P<0.05)。结论本研究筛选了DN特异性RTF关键基因,其与估算肾小球滤过率呈负相关,并可能通过免疫炎症反应途径参与DN-RTF过程。

Objective To explore the key genes of diabetic nephropathy(DN)and renal tubulointerstitial fibrosis(RTF)and examine their clinical correlations by bioinformatic analysis.Methods The datasets of renal interstitial tissue from DN and non-DN patients and renal tissue from RTF model mice were downloaded for identifying differentially expressed genes(DEGs)and screening DN specific RTF related genes.Functional enrichment and protein-protein interaction(PPI)analysis was performed for further identifying key genes.Pearson’s correlation analysis between key genes and renal function was conducted for elucidating the clinical relevance of the key genes.Results A total of 125 DN specific RTF related genes were identified.Biological function enrichment analysis showed that the above genes were correlated with immune response and metabolic process and became enriched in Toll-like receptor,NF-kappa B,tumor necrosis factor(TNF)and chemokine pathways.Based upon PPI network analysis,ITGAM,TLR2,LCP2,TLR7 and IL10RA were identified as key genes.Fold change of gene expression level was significantly higher in DN group than that in control group.And the area under curve(AUC)was 1,0.925,0.9583,0.9583 and 0.8833 respectively(P<0.01).Pearson’s correlation coefficients(r value)between gene expression level of key genes and estimated glomerular filtration rate(eGFR)were-0.7956,-0.6463,-0.752,-0.7136 and-0.7721 respectively(P<0.05).Conclusion Key genes correlated with DN specific RTF are identified.Negatively correlated with eGFR,they may participate in the process of DN-RTF through immune-inflammatory responses.