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. 2022 Jul 12:13:864407.
doi: 10.3389/fendo.2022.864407. eCollection 2022.

Screening of the Key Genes and Signalling Pathways for Diabetic Nephropathy Using Bioinformatics Analysis

Zukai Li  1   2 , Junxia Feng  3 , Jinting Zhong  1 , Meizhi Lu  1   2 , Xuejuan Gao  4 , Yunfang Zhang  1   2
Affiliations

Screening of the Key Genes and Signalling Pathways for Diabetic Nephropathy Using Bioinformatics Analysis

Zukai Li et al. Front Endocrinol (Lausanne). .

Abstract

Background: This study aimed to identify biological markers for diabetic nephropathy (DN) and explore their underlying mechanisms.

Methods: Four datasets, GSE30528, GSE47183, GSE104948, and GSE96804, were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the "limma" package, and the "RobustRankAggreg" package was used to screen the overlapping DEGs. The hub genes were identified using cytoHubba of Cytoscape. Logistic regression analysis was used to further analyse the hub genes, followed by receiver operating characteristic (ROC) curve analysis to predict the diagnostic effectiveness of the hub genes. Correlation analysis and enrichment analysis of the hub genes were performed to identify the potential functions of the hub genes involved in DN.

Results: In total, 55 DEGs, including 38 upregulated and 17 downregulated genes, were identified from the three datasets. Four hub genes (FN1, CD44, C1QB, and C1QA) were screened out by the "UpSetR" package, and FN1 was identified as a key gene for DN by logistic regression analysis. Correlation analysis and enrichment analysis showed that FN1 was positively correlated with four genes (COL6A3, COL1A2, THBS2, and CD44) and with the development of DN through the extracellular matrix (ECM)-receptor interaction pathway.

Conclusions: We identified four candidate genes: FN1, C1QA, C1QB, and CD44. On further investigating the biological functions of FN1, we showed that FN1 was positively correlated with THBS2, COL1A2, COL6A3, and CD44 and involved in the development of DN through the ECM-receptor interaction pathway. THBS2, COL1A2, COL6A3, and CD44 may be novel biomarkers and target therapeutic candidates for DN.

Keywords: FN1; bioinformatic analysis; biomarkers; diabetic nephropathy; differentially expressed genes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The volcano plot of DEGs with consistency from GSE30528 (A), GSE47183 (B), and GSE104948 (C). DEGs, differentially expressed genes.
Figure 2
Figure 2
The heatmap of clustering analysis of DEGs with consistency from GSE30528 (A), GSE47183 (B), and GSE104948 (C). DEGs, differentially expressed genes.
Figure 3
Figure 3
Ten upregulated and downregulated DEGs of the three datasets determined by “RRA.” DEGs, differentially expressed genes.
Figure 4
Figure 4
The PPI network of overlapping DEGs of three microarray datasets. Circles represent genes, lines represent interactions between gene-encoded proteins, and line thickness represents confidence in interactions between proteins. PPI, protein–protein interaction; DEGs, differentially expressed genes.
Figure 5
Figure 5
Ten algorithms to screen hub genes by “UpSetR” package.
Figure 6
Figure 6
(A) The expression of FN1 in GSE96804. (B) ROC curve of FN1 in GSE96804. ROC, receiver operating characteristic.
Figure 7
Figure 7
GO enrichment result of top 50 genes. (A) The results of GO were presented by bar plot. The x‐axis represents gene ratio, and y‐axis represents GO terms. The size of circle represents gene count. Different colours of circles represent different adjusted p-values. (B) The results of GO are presented by circle charts. Different colours of circles represent different correlation coefficients. GO, Gene Ontology.
Figure 8
Figure 8
KEGG enrichment result of top 50 genes. (A) The results of KEGG were presented by bar plot. (B) The circle charts present the results of KEGG. Different colours of the circle represent different correlation coefficients.
Figure 9
Figure 9
The correlation between FN1 and COL6A3 (A), COL1A2 (B), THBS2 (C), and CD44 (D).
Figure 10
Figure 10
Gene Set Enrichment Analysis (GSEA). The pathway related to FN1.
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