--- - |2- In this study, a total of nine genes were found to have an important function in the occurrence and development of DN, among which six were reported earlier, and the result was further verified in this study. More important, the three remaining genes, VAV1, LCK, and PLK1, were identified as novel and had the potential to serve as the predictive indicator in the diagnosis and treatment of DN, which still needs further research. Diabetic nephropathy (DN) is one of the most serious and dangerous chronic complications caused by diabetes mellitus, and the identification and development of novel biomarkers could be beneficial for the diagnosis and prognosis of DN patients. This study focused on researching the differently expressed pattern of the DN samples from glomeruli and tubulointerstitium. Significance analysis of microarrays (SAM) was used to identify differentially regulated genes in 44 microdissected human kidney samples. Functional enrichment analysis was used to analyze the functions these genes are mostly enriched in. Besides, protein–protein interaction (PPI) network was used to select the hub genes that were associated with DN. The gene expression pattern of DN samples from glomeruli and tubulointerstitium was found to be quite different. It showed that the recurrence rate of DN originating from glomeruli and control samples was lower than that from tubulointerstitium and control samples. A total of 332 differentially expressed genes were identified between glomeruli tissues and tubulointerstitium tissues. PPI network analysis was performed on these 332 genes. Finally, nine hub genes were selected as the most potential biomarkers in the occurrence of DN. In conclusion, a total of 332 genes were found to be related to DN, and these genes were found to be mostly enriched in pathways such as immunity, inflammatory, and vascular pathways. Three genes VAV1, LCK, and Plk had the potential to serve as indicators for the occurrence and development of DN in clinical management. - 'Journal of Cellular Physiology, Volume 234, Issue 2, Page 1461-1468, February 2019. '