Identification of pathogenic genes and transcription factors in vitiligo

Our study aimed to identify the key genes and upstream regulators in vitiligo. To screen the pathogenic genes of vitiligo, an integrated analysis was performed by using the microarray datasets in vitiligo derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were further explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We constructed a vitiligo-specific transcriptional regulatory network to identify crucial transcriptional factors that target the DEGs in vitiligo. From two GEO datasets, we identified 1863 DEGs (744 downregulated DEGs and 1,119 upregulated DEGs [false discovery rate < 0.05, |Combined.ES| > 1]) between lesional tissues and nonlesional tissues. GO and KEGG analyses revealed that ubiquitin-mediated proteolysis and the endoplasmic reticulum were significantly enriched pathways for DEGs. The expressions of premelanosome (PMEL), melan-A (MLANA), dopachrome tautomerase (DCT), SRY-boxtranscription factor 10 (SOX10), tyrosinase-related protein 1 (TYRP1), and melanocortin 1 receptor (MC1R) were shown to be involved in the pathogenesis of vitiligo. We concluded that PMEL, MLANA), DCT, SOX10, TYRP1, and MC1R may play a role in vitiligo, among which TYRP1 and MC1R are regulated by forkhead box J2 (FOXJ2). Our finding may contribute to the development of new potential biomarkers, reveal the underlying pathogenesis of vitiligo, and identify novel therapeutic targets for vitiligo.