Systematic Identification of Core Targets ABCB1, PIM2, and TSHR Mediating Bisphenol S-Promoted Cutaneous Melanoma Metastasis and Prognostic Model Construction

Background: Cutaneous melanoma is the most aggressive malignant skin tumor, and metastasis represents the primary cause of patient mortality. Bisphenol S (BPS) has an unclear influence on melanoma metastasis and its underlying molecular mechanisms. Methods: Potential BPS targets were predicted using the SEA, SwissTargetPrediction, and SuperPred databases. Based on TCGA-SKCM transcriptomic data, differential expression analysis was performed, and Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct a gene co-expression network. Candidate genes were obtained by integrating BPS-related targets, differentially expressed genes (DEGs), module genes, and univariate Cox regression genes, followed by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network construction. Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression was applied to screen core prognostic genes and construct a risk prediction model. Further analyses included network construction, molecular docking, and 100 ns molecular dynamics (MD) simulation. Results: Integration of BPS-related targets, DEGs, WGCNA module genes, and Cox regression results yielded 13 candidate genes enriched in kinase activity regulation and melanoma-related pathways. LASSO-Cox regression ultimately identified three core prognostic genes--ABCB1, PIM2, and TSHR--all significantly upregulated in metastatic tissues, with area under the curve (AUC) values of approximately 0.7. High-expression patients exhibited significantly better overall survival than low-expression patients (P < 0.05). A nomogram incorporating the three genes and clinical parameters demonstrated good calibration performance. Within the ceRNA network, MALAT1 and hsa-miR-155-5p were identified as key regulatory molecules, and 37 potential transcription factors were predicted, including CEBPA, JUN, and STAT3. Molecular docking revealed strong binding affinities of BPS toward ABCB1 , PIM2, and TSHR, and MD simulations confirmed the structural stability of all three complexes. Conclusion: ABCB1, PIM2, and TSHR are the core target genes through which BPS influences melanoma metastasis via multidrug resistance, kinase signaling, and receptor-mediated signal transduction. The prognostic model based on these three genes demonstrates good clinical applicability, and the ceRNA and transcription factor regulatory networks provide a systematic molecular basis for understanding the association between BPS exposure and melanoma metastasis.