Association and Mechanistic Insights Linking Bisphenol A to Psoriasis: Integrative Analysis of Bulk Transcriptomics, Network Toxicology, Mendelian Randomization and Single‑cell RNA Sequencing.

Purpose: Psoriasis is a chronic immune-mediated skin disease with complex etiology, and environmental factors such as bisphenol A (BPA) exposure are suspected pathogenic factors. This study aimed to identify potential diagnostic biomarkers linking BPA exposure to psoriasis and to explore the latent interaction and mechanisms between BPA and candidate biomarkers. Patients and Methods: Psoriasis-related transcriptomic datasets (GSE14905, GSE13355, GSE183047) were downloaded from the Gene Expression Omnibus (GEO) database, and psoriasis-related genome-wide association study (GWAS) data were obtained from the GWAS Catalog. Target genes of psoriasis and BPA were retrieved from multiple public databases. A multi-omics integrative strategy was adopted in this study, combining bulk transcriptomics, network toxicology, Mendelian randomization, and single-cell RNA sequencing (scRNA-seq). Computational molecular binding prediction and in vivo animal experiments were further performed for biomarker validation. Results: PSMD1 and BECN1 were identified as potential biomarkers linking BPA exposure to psoriasis, showing significant upregulation in the psoriasis group and high diagnostic accuracy. Gene Set Enrichment Analysis (GSEA) revealed the involvement of these molecules in several key pathways, such as proteasome and oxidative phosphorylation. Immune infiltration analysis reported a positive correlation between these biomarkers and M1-type macrophage cell frequency, while stable binding capacity was predicted between biomarkers and BPA. scRNA-seq identified dendritic cells (DCs) as key immune cells, characterized by increased cell-cell communication in the psoriasis group. Moreover, pseudo-time trajectory analysis showed that PSMD1 exhibited elevated expression at the terminal stage of DC differentiation, whereas BECN1 displayed increased expression at both the early and terminal stages. In vivo experiments confirmed a dose-dependent effect of BPA exposure on the severity of psoriasis-like inflammation, followed by an increased expression of both PSMD1 and BECN1. Conclusion: This study identifies PSMD1 and BECN1 as potential diagnostic biomarkers associated with BPA exposure and psoriasis, offers predictive insights into their possible roles in related pathways and immune regulation, and sheds light on molecular-cellular mechanisms linking BPA exposure to psoriasis pathogenesis.