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. 2020 Sep;8(17):1087.
doi: 10.21037/atm-20-5647.

Investigation of hub genes involved in diabetic nephropathy using biological informatics methods

Zhanting Li  1 , Jianxin Liu  2 , Weiwei Wang  3 , Yunchun Zhao  4 , Dengfeng Yang  5 , Xiaodong Geng  6   7
Affiliations

Investigation of hub genes involved in diabetic nephropathy using biological informatics methods

Zhanting Li et al. Ann Transl Med. 2020 Sep.

Abstract

Background: The aim of this study was to find genes with significantly aberrant expression in diabetic nephropathy (DN) and determine their underlying mechanisms.

Methods: GSE30528 and GSE1009 were obtained by querying the Gene Expression Omnibus (GEO) database. The difference in target gene expression between normal renal tissues and kidney tissues in patients with DN was screened by using the GEO2R tool. Using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, differentially expressed genes (DEGs) were analysed by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then, the protein-protein interactions (PPIs) of DEGs were analyzed by Cytoscape with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the hub genes in this PPI network were recognized by centrality analysis.

Results: There were 110 genes with significant expression differences between normal and DN tissues. The differences in gene expression involved many functions and expression pathways, such as the formation of the extracellular matrix and the construction of the extracellular domain. The correlation analysis and subgroup analysis of 14 hub genes and the clinical characteristics of DN showed that CTGF, ALB, PDPN, FLT1, IGF1, WT1, GJA1, IGFBP2, FGF9, BMP2, FGF1, BMP7, VEGFA, and TGFBR3 may be involved in the progression of DN.

Conclusions: We confirmed the differentially expressed hub genes and other genes which may be the novel biomarker and target candidates in DN.

Keywords: Diabetic nephropathy (DN); bioinformatics analysis; differentially expressed gene (DEG); hub genes; microarray analysis.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5647). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Identification of 110 commonly changed DEGs from the two cohort profile datasets (GSE30528 and GSE1009). Different color areas represent different datasets. The cross areas indicate commonly changed DEGs. DEGs, differentially expressed genes.
Figure 2
Figure 2
Common DEGs PPI network constructed by STRING online database and Module analysis. (A) There were a total of 110 DEGs in the DEG PPI network complex. The nodes represent proteins, and the edges represent the interaction of proteins. Green circles represent downregulated DEGs, and red circles represent upregulated DEGs. (B) Module analysis for PPI network of gene signatures via Cytoscape software. Green represents a downregulated gene. DEGs, differentially expressed genes; PPI, protein-protein interaction; STRING, Search Tool for the Retrieval of Interacting Genes/Proteins.
Figure 3
Figure 3
Hub genes and their co-expressed genes were analyzed using Coexpedia. Nodes with red background represent the co-expressed genes.
Figure 4
Figure 4
Correlation between mRNA expression of upregulated hub genes in GFR in DN patients. GFR, glomerular filtration rate; DN, diabetic nephropathy.
Figure 5
Figure 5
Association between the expression of unexplored hub genes and proteinuria in DN patients. DN, diabetic nephropathy.
See this image and copyright information in PMC

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