Exploring the molecular interface of gene expression dynamics and prostate cancer susceptibility in response to HBCD exposure.

Abstract

Hexabromocyclododecane (HBCD), a brominated flame retardant, is linked to various health implications, including prostate cancer. This study explored the molecular mechanisms and potential biomarkers associated with HBCD exposure using data from the Comparative Toxicogenomics Database (CTD) and The Cancer Genome Atlas (TCGA). A total of 7,147 differentially expressed genes (DEGs) and 46 differentially expressed miRNAs were identified, with significant enrichment in cancer-related pathways and xenobiotic metabolism. Protein-protein interaction (PPI) network construction and enrichment analyses revealed four hub genes: DNAJC12, PKMYT1, RRM2, and SLC12A5. These genes displayed notable expression changes in response to HBCD exposure and were strongly correlated with survival outcomes in prostate cancer patients, as demonstrated by Cox regression and ROC curve analyses. Additionally, miRNA correlation analyses indicated robust positive associations, highlighting a coordinated regulatory network. Experimental expression analyses on HBCD-treated cell lines further validated these findings. This study sheds light on the significant impact of HBCD on gene and miRNA expression in prostate cancer, emphasizing the potential of the identified hub genes and miRNAs as prognostic biomarkers and therapeutic targets. By elucidating the pathways and regulatory networks influenced by HBCD, the findings provide a foundation for developing strategies to mitigate its carcinogenic effects and improve outcomes for prostate cancer patients.