Transcriptomic and functional analysis of triphenyl phosphate exposure in prostate cancer progression

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BACKGROUND: Prostate cancer is a common malignancy in men with variable clinical outcomes. While therapeutic options have improved, the potential impact of environmental chemicals such as Triphenyl phosphate (TPP)-a widely used organophosphorus flame retardant-on prostate cancer progression remains poorly understood. METHODS: We conducted transcriptomic profiling using mRNA sequencing to investigate gene expression changes in prostate cancer cells following TPP exposure. Subsequent analyses, including single-sample gene set enrichment analysis (ssGSEA) and data mining from the Comparative Toxicogenomics Database (CTD), were performed to identify TPP-associated genes. TCGA-based survival modeling was used to evaluate the prognostic relevance of selected genes. Functional assays were carried out to assess TPP-induced phenotypic changes. RESULTS: Exposure to 0.1 µM TPP significantly enhanced prostate cancer cell proliferation and invasion. Transcriptomic analysis revealed 521 upregulated and 964 downregulated genes post-treatment. Key prognostic markers, including TTK, S100A9, MACIR, AKR1B10P1, and ZFPM2-AS1, were identified and found to be associated with poor patient survival. GSEA further revealed that these genes are enriched in pathways related to metabolism and cancer progression. CONCLUSION: Our findings suggest that TPP exposure may promote malignant phenotypes in prostate cancer cells by altering gene expression and activating cancer-associated pathways. This study underscores the potential health risks of environmental pollutants and highlights candidate prognostic biomarkers in prostate cancer.

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