Analysis of key genes and their functions in placental tissue of patients with gestational diabetes mellitus

Abstract

Background: This study was aimed at screening out the potential key genes and pathways associated with gestational diabetes mellitus (GDM).

Methods: The GSE70493 dataset used for this study was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in the placental tissue of women with GDM in relation to the control tissue samples were identified and submitted to protein-protein interaction (PPI) network analysis and subnetwork module mining. Functional enrichment analyses of the PPI network and subnetworks were subsequently carried out. Finally, the integrated miRNA-transcription factor (TF)-DEG regulatory network was analyzed.

Results: In total, 238 DEGs were identified, of which 162 were upregulated and 76 were downregulated. Through PPI network construction, 108 nodes and 278 gene pairs were obtained, from which chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, protein tyrosine phosphatase, receptor type C (PTPRC), and human leukocyte antigen (HLA) were screened out as hub genes. Moreover, genes associated with the immune-related pathway and immune responses were found to be significantly enriched in the process of GDM. Finally, miRNAs and TFs that target the DEGs were predicted.

Conclusions: Four candidate genes (viz., CXCL9, CXCL10, PTPRC, and HLA) are closely related to GDM. miR-223-3p, miR-520, and thioredoxin-binding protein may play important roles in the pathogenesis of this disease.

Keywords: Differentially expressed genes; Gestational diabetes mellitus; Integrated regulatory network; Protein-protein interaction network; Transcription factors.

Fig. 1

Volcano map of the distribution of differentially expressed genes. Each blue dot represents a differentially expressed gene

Fig. 2

GO and KEGG pathway enrichment analyses of the differentially expressed genes. a Gene Ontology (GO) enrichment analysis of the top 10 differentially expressed genes (DEGs) by p-value. BP: Biological process; MF: molecular function; CC: cellular component; Counts: the number of enriched DEGs; Black trend line: -log₁₀ (p-adjust)/2; P-adjust: rectified p-value. b Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs. Rich factor: the ratio of the number of enriched DEGs in the KEGG category to the total genes in that category. The larger the Rich factor, the higher the degree of enrichment

Fig. 3

Protein-protein interaction network of the differentially expressed genes. The red square node represents upregulated genes; the blue circular node represents downregulated genes

Fig. 4

Two subnetwork modules of the differentially expressed genes. a Module 1 subnetwork diagram; b module 2 subnetwork diagram. The red square nodes represent upregulated genes; the blue round nodes represent downregulated genes

Fig. 5

GO and KEGG pathway enrichment analyses of the differentially expressed genes in two subnetwork modules. a Gene Ontology (GO) enrichment analysis of the differentially expressed genes (DEGs) in the two subnetwork modules. GeneRatio: the ratio of the number of lncRNA target genes in the GO category to that of the annotated genes (counts below the horizontal axis) in the GO database. The horizontal coordinate is the lncRNA, and the ordinate is the name of the GO category. b Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs in the two subnetwork modules. GeneRatio: the ratio of the number of lncRNA target genes in the KEGG category to that of the annotated genes (counts below the horizontal axis) in the KEGG database. The horizontal coordinate is the lncRNA, and the ordinate is the name of the KEGG item

Fig. 6

Constructed interaction network of the differentially expressed genes. The red square nodes are upregulated genes; the blue circle nodes are downregulated genes; the purple v-shaped frames are transcription factors (TFs); and the purple triangles are miRNAs