Identification of hub genes associated with accumulation of extracellular matrix as biomarkers of diabetic nephropathy

Abstract

<jats:title>Abstract</jats:title> <jats:p>Background Diabetic nephropathy (DN) remains a major cause of end stage renal disease (ESRD). The development of novel biomarkers and early diagnosis of DN are of great clinical importance. The goal of this study was to identify hub genes with diagnostic potential for DN by weighted gene co-expression network analysis (WGCNA). Methods Gene Expression Omnibus (GEO) database was searched for microarray data including distinct types of chronic kidney diseases (CKD). Gene co-expression network was constructed and modules specific for DN were identified by WGCNA. Gene Ontology (GO) analysis was performed and the hub genes were screened out within the selected gene modules. Furthermore, receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic values of hub genes. In addition, an external validation was performed in an independent dataset. Results Dataset GSE99339 was selected and a total of 179 microdissected glomeruli samples were analyzed, including DN, normal control and 7 groups of other glomerular diseases. 23 modules of the total 10947 genes were grouped by WGCNA and a module was specifically correlated with DN (<jats:italic>r</jats:italic> = 0.54, 9e-15). GO analysis showed that module genes were mainly enriched in the accumulation of extracellular matrix (ECM). LUM, ELN, FBLN1, MMP2, FBLN5 and FMOD were identified as hub genes. Furthermore, levels of hub genes were the highest in DN compared to other groups, which could differentially diagnose DN (AUC, 0.67 ~ 0.95). External verification showed hub genes were higher in DN group and were negatively correlated with eGFR. Conclusions By using WGCNA approach, we identified 6 hub genes, LUM, ELN, FBLN1, MMP2, FBLN5 and FMOD, related to ECM accumulation and were specific for DN. These genes may represent potential candidate diagnostic biomarkers of DN.</jats:p>