Transcriptomic landscaping of core genes and pathways of mild and severe psoriasis vulgaris

Abstract

Psoriasis is a common chronic inflammatory skin disease affecting >125 million individuals worldwide. The therapeutic course for the disease is generally designed upon the severity of the disease. In the present study, the gene expression profile GSE78097, was retrieved from the National Centre of Biotechnology (NCBI)‑Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) in mild and severe psoriasis using the Affy package in R software. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways of the DEGs were analysed using clusterProfiler, Bioconductor, version 3.8. In addition, the STRING database was used to develop DEG‑encoded proteins and a protein‑protein interaction network (PPI). Cytoscape software, version 3.7.1 was utilized to construct a protein interaction association network and analyse the interaction of the candidate DEGs encoding proteins in psoriasis. The top 2 hub genes in Cytohubba plugin parameters were validated using immunohistochemical analysis in psoriasis tissues. A total of 382 and 3,001 dysregulated mild and severe psoriasis DEGs were reported, respectively. The dysregulated mild psoriasis genes were enriched in pathways involving cytokine‑cytokine receptor interaction and rheumatoid arthritis, whereas cytokine‑cytokine receptor interaction, cell cycle and cell adhesion molecules were the most enriched pathways in severe psoriasis group. PL1N1, TLR4, ADIPOQ, CXCL8, PDK4, CXCL1, CXCL5, LPL, AGT, LEP were hub genes in mild psoriasis, whereas BUB1, CCNB1, CCNA2, CDK1, CDH1, VEGFA, PLK1, CDC42, CCND1 and CXCL8 were reported hub genes in severe psoriasis. Among these, CDC42, for the first time (to the best of our knowledge), has been reported in the psoriasis transcriptome, with its involvement in the adaptive immune pathway. Furthermore, the immunoexpression of CDK1 and CDH1 proteins in psoriasis skin lesions were demonstrated using immunohistochemical analysis. On the whole, the findings of the present integrated bioinformatics and immunohistochemical study, may enhance our understanding of the molecular events occurring in psoriasis, and these candidate genes and pathways together may prove to be therapeutic targets for psoriasis vulgaris.

Keywords: psoriasis; psoriasis vulgaris; differentially expressed gene; hub genes; cytoscape.

Figure 1

(A) Volcano plot showing DEGs between mild psoriasis and normal samples, (B) volcano plot showing DEGs between severe psoriasis and normal samples, (C) Venn diagram representing DEGs in both severe (blue colour) and mild (yellow colour) group. The intersection part represents the shared DEGS between both the groups. DEGs, differentially expressed genes.

Figure 2

Heatmap of top 20 dysregulated (10 upregulated and 10 downregulated) DEGs represents expression of (A) mild psoriasis DEGs (B) severe psoriasis DEGs. Red colour signifies upregulation and blue signifies the downregulation of DEGs. DEGs, differentially expressed genes.

Figure 3

The principal component plot of top 20 dysregulated genes. (A) Mild psoriasis, (B) severe psoriasis of 33 samples distinguishes the DEGS between the sample sub-types. DEGs, differentially expressed genes.

Figure 4

Gene ontology (GO) analysis and significant GO terms of DEGs in mild and severe psoriasis. (A) GO analysis classified the mild psoriasis DEGs, (B) GO analysis classified the severe psoriasis DEGs into 3 groups (i.e., biological process, molecular function, and cellular component). Yellow bars represent biological process, red bars molecular function and purple bars cellular component. DEGs, differentially expressed genes.

Figure 5

Significantly enriched pathway terms of DEGs. (A) Mild psoriasis, and (B) severe psoriasis. DEGs functional and signalling pathway enrichment was conducted using online website of KEGG Pathway in clusterProfiler. DEGs, differentially expressed genes.

Figure 6

Gene disease network of the differentially expressed genes. (A) Mild-psoriasis vulgaris sub type. (B) Severe-psoriasis vulgaris sub type.

Figure 7

Top 10 hub genes with DEGs degree from the PPI network. (A) Mild psoriasis. (B) Severe psoriasis.

Figure 8

CDK1 immunoreactivity in psoriatic skin lesions and non-lesional samples. CDK1 immunoexpression and localization (blue and green arrows) in (A and B) psoriatic skin lesions and (C and D) non-lesional or normal skin tissue; magnification ×40.

Figure 9

CDH1 immunoreactivity in human psoriatic skin tissue. CDH1 immunoexpression and localization (blue and green arrows) in (A and B) psoriatic skin lesions and (C and D) non-lesional or normal skin tissue; magnification ×40.