Integrative bioinformatics and experimental validation identify PRICKLE1 as a potential biomarker in keloids

Keloids are chronic fibrotic inflammatory lesions located in the reticular dermis that are characterized by abnormal fibroblast proliferation and excessive collagen deposition. Owing to the unclear pathogenesis of keloids, there is a lack of universally effective treatment options in clinical practice. To identify potential pathogenic genes and explore the mechanisms of keloid formation, we analyzed fibroblast data from the publicly available GSE44270 dataset in the Gene Expression Omnibus (GEO) database after batch effect correction. Weighted gene coexpression network analysis (WGCNA), differential expression analysis, protein-protein interaction (PPI) network construction, and random forest modeling were applied to fibroblast expression profiles to identify candidate hub genes and investigate their functional. WGCNA combined with PPI network analysis identified 50 candidate genes, whereas differential expression analysis combined with random forest modeling identified 10 candidate genes. The intersection of these two gene sets revealed PRICKLE1 as the hub gene. The expression of PRICKLE1 was validated in the GSE7890, and clinical specimen using qPCR ( P < 0.01) and WB ( P < 0.01). Further gene set enrichment analysis suggested that PRICKLE1 may be associated with arachidonic acid metabolism, extracellular matrix-receptor interactions, cell adhesion, and Hedgehog signaling. The above results suggest that there appears to be a certain association between PRICKLE1 and keloids. This association may help us gain a more comprehensive understanding of the pathogenesis of the disease and could potentially provide a reference for future treatment decisions.