Psoriasis features keratinocyte hyperproliferation. This study aimed to identify disulfidptosis-related key genes in psoriasis for potential diagnostic biomarkers or therapeutic targets. Using the GSE30999 dataset, WGCNA was applied to identify key gene modules. GO, KEGG were used for analysis. IHC, Western blot, PCR and free thiol tests verified results. WGCNA clustered differentially expressed genes into 18 modules, with the blue module being significantly associated with psoriasis (Pearson's r = 0.82, P < 0.001). Six hub genes (FRK, GYS1, HECW2, MYH10, S100A12, SLC7A11) were identified. GYS1, S100A12, and SLC7A11 showed pronounced dysregulation (FDR < 0.01) and upregulation in psoriasis epidermis (P < 0.05). The double-stranded death core pathogenic gene SLC7A11 can regulate the level of free sulfhydryl groups and the expression levels of molecules in the NF-κB pathway.(P < 0.05). GYS1, S100A12, and SLC7A11 are disulfidptosis-related driver genes in psoriasis, aiding molecular diagnosis and treatment.
