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. 2022 Dec 31:2022:1067504.
doi: 10.1155/2022/1067504. eCollection 2022.

Identification of Oxidative Stress-Related Biomarkers in Diabetic Kidney Disease

Xiaoju Ma  1   2 , Xiaobo Zhang  1 , Tian Leng  2 , Jingru Ma  2 , Zhongzhu Yuan  2 , Yalin Gu  2 , Tingting Hu  2 , Qiuyan Liu  2 , Tao Shen  1
Affiliations

Identification of Oxidative Stress-Related Biomarkers in Diabetic Kidney Disease

Xiaoju Ma et al. Evid Based Complement Alternat Med. .

Abstract

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease throughout the world. In kidney disease, oxidative stress has been linked to both antioxidant depletions and increased reactive oxygen species (ROS) production. Thus, the objective of this study was to identify biomarkers related to oxidative stress in DKD.

Methods: The gene expression profile of the DKD was extracted from the Gene Expression Omnibus (GEO) database. The identification of the differentially expressed genes (DEGs) was performed using the "limma" R package, and weighted gene coexpression network analysis (WGCNA) was used to find the gene modules that were most related to DKD. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using "Org.Hs.eg.db" R package. The protein-protein interaction (PPI) network was constructed using the STRING database. The hub genes were identified by the Molecular Complex Detection (MCODE) plug-in of Cytoscape software. The diagnostic capacity of hub genes was verified using the receiver operating characteristic (ROC) curve. Correlations between diagnostic genes were analyzed using the "corrplot" package. In addition, the miRNA gene transcription factor (TF) network was used to explain the regulatory mechanism of hub genes in DKD.

Results: DEGs analysis and WGCNA-identified 160 key genes were identified in DKD patients. Among them, nine oxidative stress-related genes were identified as candidate hub genes for DKD. Using the PPI network, five hub genes, NR4A2, DUSP1, FOS, JUN, and PTGS2, were subsequently identified. All the hub genes were downregulated in DKD and had a high diagnostic value of DKD. The regulatory mechanism of hub genes was analyzed from the miRNA gene-TF network.

Conclusion: Our study identified NR4A2, DUSP1, FOS, JUN, and PTGS2 as hub genes of DKD. These genes may serve as potential therapeutic targets for DKD patients.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The differential expression genes identified by the “limma” R package between DKD tissue and normal tissue in the GSE142025. (a) Volcano plot for the differential expression analysis, blue dots are for downregulated and red for upregulated genes. (b) Heatmap for the top 10 upregulated genes and top 10 downregulated genes as sorted by the adjusted p value.
Figure 2
Figure 2
Construction of coexpression modules related to DKD based on WGCNA. (a) Sample clustering to detect outliers. (b) Sample clustering in the DKD tissue and normal tissue. (c) The appropriate soft threshold selection. (d) Coexpression genes expression pattern of 20 modules by WGCNA analysis. (e) Correlation between coexpression modules and DKD.
Figure 3
Figure 3
Screening and analysis of key genes and candidate hub genes of DKD. (a) Venn diagram for intersections between DEGs and module genes of WGCNA. (b) Genes set enrichment analysis of 160 key genes by the Hallmark gene database. (c)–(e) GO enrichment map in BP, CC, and MF. (f) KEGG enrichment map.
Figure 4
Figure 4
PPI network diagram of hub genes related oxidative stress. (a) PPI network diagram of 9 candidate hub genes. (b) PPI network diagram of 5 hub genes from core module analyzed using MCODE. (c) Expression levels of the five hub genes.
Figure 5
Figure 5
Evaluation of the diagnostic effect of the hub gene on DKD. (a) ROC curves and AUC values of the five hub genes. (b) Correlations among the five hub genes.
Figure 6
Figure 6
Construction of the miRNA gene-TF regulatory network. Light blue rectangle represents hub genes, orange oval represents miRNA, and purple diamond represents TF.
Figure 7
Figure 7
Expression validation of the hub gene in the training set.
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