Integrated transcriptomic and tissue-validation analyses identify palmitoylation-associated biomarkers linked to sphingolipid metabolism and immune remodeling in psoriasis.

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by epidermal dysfunction, aberrant keratinocyte activation, and complex immune remodeling. Although lipid dysregulation has increasingly been implicated in psoriasis, the role of palmitoylation-associated genes in cutaneous inflammation remains insufficiently defined. Methods: We integrated bulk transcriptomic datasets (GSE14905, GSE13355, and GSE121212) and a single-cell RNA-sequencing dataset (GSE151177) to identify palmitoylation-associated biomarkers in psoriasis. Weighted gene co-expression network analysis, differential expression analysis, and machine-learning algorithms including LASSO and SVM-RFE were applied to screen hub genes. Functional enrichment, immune microenvironment analysis, regulatory-network construction, and candidate-drug prediction were subsequently performed. In addition, RT-qPCR was used to validate the expression of candidate genes in psoriatic lesional skin and healthy control skin. Results: We identified 209 palmitoylation-associated differentially expressed genes and screened five candidate hub genes: Conclusion: This study identifies a palmitoylation-associated molecular signature related with sphingolipid metabolism, keratinocyte activation, and immune remodeling in psoriasis. These findings not only provide candidate biomarkers for disease stratification, but also highlight potentially druggable pathways and therapeutic targets for future translational investigation.