Bioinformatics Identification of Ferroptosis-Associated Biomarkers and Therapeutic Compounds in Psoriasis

PURPOSE: Psoriasis is closely linked to ferroptosis. This study aimed to identify potential ferroptosis-associated genes in psoriasis using bioinformatics. METHODS: Data from the GSE30999 dataset was downloaded from the Gene Expression Omnibus (GEO), and the ferroptosis-associated genes were retrieved from FerrDb. The differentially expressed ferroptosis-associated genes were identified using Venn diagrams. Subsequently, a network of protein-protein interactions (PPIs) between psoriasis targets and ferroptosis-associated genes was constructed based on the STRING database and analyzed by Cytoscape software. The Metascape portal conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Moreover, the expression of ferroptosis-related genes was verified in the GSE13355 dataset. Finally, the verified genes were used to predict the therapeutic drugs for psoriasis using the DGIdb/CMap database. SwissDock was used to examine ligand docking, and UCSF Chimera displayed the results visually. RESULTS: Among 85 pairs of psoriasis lesion (LS) and no-lesion (NL) samples from patients, 19 ferroptosis-associated genes were found to be differentially expressed (3 upregulated genes and 16 downregulated genes). Based on the PPI results, these ferroptosis-associated genes interact with each other. The GO and KEGG enrichment analysis of differentially expressed ferroptosis-related genes indicated several enriched terms related to the oxidative stress response. The GSE13355 dataset verified the results of the bioinformatics analysis obtained from the GSE30999 dataset regarding SLC7A5, SLC7A11, and CHAC1. Psoriasis-related compounds corresponding to SLC7A5 and SLC7A11 were also identified, including Melphalan, Quisqualate, Riluzole, and Sulfasalazine. CONCLUSION: We identified 3 differentially expressed ferroptosis-related genes through bioinformatics analysis. SLC7A5, SLC7A11, and CHAC1 may affect the development of psoriasis by regulating ferroptosis. These results open new avenues in understanding the treatment of psoriasis.