Abstract
BackgroundThe aim of this study was to identify the candidate biomarkers and pathways associated with psoriasis. GSE13355 and GSE14905 were extracted from the Gene Expression Omnibus (GEO) database. Then the differentially expressed genes (DEGs) with |logFC| > 2 and adjusted P < 0.05 were chosen. In addition, the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for DEGs were performed. Then, the GO terms with P < 0.05 and overlap coefficient greater than 0.5 were integrated by EnrichmentMap. Additionally, risk subpathways analysis for DEGs was also conducted by using the iSubpathwayMiner package to obtain more psoriasis-related DEGs and pathways. Finally, protein-protein interaction (PPI) network analysis was performed to identify the hub genes, and the DGIdb database was utilized to search for the candidate drugs for psoriasis.ResultsA total of 127 DEGs which were mostly associated with keratinization, keratinocyte differentiation, and epidermal cell differentiation biological processes were identified. Based on these GO terms, 3 modules (human skin, epidermis and cuticle differentiation, and enzyme activity) were constructed. Moreover, 9 risk subpathways such as steroid hormone biosynthesis, folate biosynthesis, and pyrimidine metabolism were screened. Finally, PPI network analysis demonstrated that CXCL10 was the hub gene with the highest degree, and CXCR2, CXCL10, IVL, OASL, and ISG15 were the potential gene targets of the drugs for treating psoriasis.ConclusionPsoriasis may be mostly caused by keratinization, keratinocyte differentiation, and epidermal cell differentiation; the pathogeneses were more related with pathways such as steroid hormone biosynthesis, folate biosynthesis, and pyrimidine metabolism. Besides, some psoriasis-related genes such as SPRR genes, HSD11B1, GGH, CXCR2, IVL, OASL, ISG15, and CXCL10 may be important targets in psoriatic therapy.
Highlights
The aim of this study was to identify the candidate biomarkers and pathways associated with psoriasis
Biological processes of differentially expressed genes (DEGs) were mostly associated with keratinization (GO: 0031424), keratinocyte differentiation (GO: 0030216), and epidermal cell differentiation (GO: 0009913)
A recent study suggested that the decrease in serum CXCL10 level over time was related to the new onset of psoriatic arthritis in patients with psoriasis [24], and our study revealed a same result that CXCL10 was up-regulated in psoriasis
Summary
The aim of this study was to identify the candidate biomarkers and pathways associated with psoriasis. Protein-protein interaction (PPI) network analysis was performed to identify the hub genes, and the DGIdb database was utilized to search for the candidate drugs for psoriasis. Psoriasis is not purely a skin disorder and it may affect many other organs and cause other diseases [2,3,4]. Previous studies have reported that psoriasis is generally caused by aberrant keratinocyte proliferation and differentiation, epidermal hyperplasia, angiogenesis, dendritic cells and neutrophils, infiltration of T lymphocytes, and elements of innate immunity [7]. Many studies focused on the identification of psoriasis susceptibility loci which were correlated with the pathogenesis. The molecular mechanisms of psoriasis remain to be fully understood
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