Integrated bioinformatic analysis of differentially expressed genes and signaling pathways in plaque psoriasis

Abstract

Psoriasis is an immune‑mediated cutaneous disorder with a high incidence and prevalence. Patients with psoriasis may experience irritation, pain and psychological problems. The cause and underlying molecular etiology of psoriasis remains unknown. In an attempt to achieve a more comprehensive understanding of the molecular pathogenesis of psoriasis, the gene expression profiles of 175 pairs of lesional and corresponding non‑lesional skin samples were downloaded from 5 data sets in the Gene Expression Omnibus (GEO) database. Integrated differentially expressed genes (DEGs) were obtained with the use of R software. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed using the DAVID online analysis tool. The protein‑protein interaction (PPI) network was constructed on the STRING platform and hub genes were calculated with the use of Cytoscape software. Finally, GEO2R was used to determine the expression of the hub genes in scalp psoriasis. A total of 373 genes from the 5 data sets were identified as DEGs, including 277 upregulated and 96 downregulated genes. GO analysis revealed that immune responses and epidermal differentiation/development were the most enriched terms in biological processes, extracellular space/matrix was the most enriched term in cellular components, and endopeptidase inhibitor activity was the most enriched term in molecular functions. In the KEGG pathway enrichment, DEGs were mainly enriched in the metabolic and viral infection‑associated pathways. A total of 17 hub genes were calculated, including CSK2, CDC45, MCM10, SPC25, NDC80, NUF2, AURKA, CENPE, RRM2, DLGP5, HMMR, TTK, IFIT1, RSAD2, IFI6, IFI27 and ISG20, among which interferon‑α‑inducible genes were revealed to display a similar expression pattern as that obtained in scalp psoriasis. This comprehensive bioinformatic re‑analysis of GEO data provides new insights on the molecular pathogenesis of psoriasis and the identification of potential therapeutic targets for the treatment of psoriasis.

Figure 1.

Data standardization and DEG identification. (A) Pre-standardization gene expression levels of each data set are presented as blue boxplots and post-standardization values are presented as purple boxplots. (B) The upregulated DEGs (red dots) and downregulated DEGs (green dots) of each data set were identified with the use of criteria of P<0.05 and |log2FC|≥1. DEGs, differently expressed genes.

Figure 2.

DEG integration of each data set. DEGs of each data set are overlapped and presented as a Venn plot, including total, upregulated and downregulated genes. DEGs, differently expressed genes.

Figure 3.

GO enrichment of DEGs. (A) GO enrichment of upregulated DEGs in 3 functional groups: biological processes (red), cellular components (green) or molecular functions (blue). These groups are ranked and presented as bar plots according to their Fisher's exact P-value. (B) GO enrichment of downregulated DEGs. DEGs, differently expressed genes; GO, gene ontology.

Figure 4.

KEGG pathway enrichment of upregulated DEGs. The upregulated DEGs were mainly enriched in metabolic and viral infection KEGG pathways. Rich factor (%) is the ratio of the number of differentially expressed genes annotated in a pathway (as indicated in the y-axis) to the number of all genes annotated in this pathway. DEGs, differently expressed genes; KEGG, Kyoto Encyclopedia of Genes and Genomes.

Figure 5.

PPI network and hub genes. (A) The PPI network was constructed and formatted with upregulated genes revealed in red ellipses and downregulated genes in green ellipses. (B) Hub genes, represented as circles, were separated into 2 groups and the interaction evidence degree between proteins is presented as the gray scale of the lines. PPI, protein-protein interaction.

Figure 6.

Gene expression levels in scalp psoriasis. Hub genes with significantly different expression levels between lesional and non-lesional scalp samples are plotted. The asterisk (*) indicates statistically significant differences between non-lesional scalp and lesional scalp samples (*P<0.05, **P<0.01).