Integrative analysis reveals SRD5A2 as a central mediator in PPCPs induced modulation of the prostate cancer immune microenvironment.

backgroundPharmaceuticals and Personal Care Products (PPCPs) are an emerging class of micropollutants that have attracted increasing attention in recent years. However, their potential role in prostate cancer (PCa) remains largely unexplored. This study aims to elucidate the mechanisms by which PPCPs influence PCa progression and identify key genes involved in this process.

methodsA network toxicology approach was employed to identify PPCPs related genes associated with PCa. Bioinformatics analyses were conducted to pinpoint key genes and their underlying mechanisms. Additionally, molecular docking was performed to assess the binding affinity between PPCPs and the identified genes.

resultsThe study analyzed the relationship between 49 types of PPCPs and PCa, ultimately identifying 24 types of PPCPs that may promote the development of PCa. Network toxicology analysis identified 156 PPCPs-PCa related genes. Further screening using univariate Cox regression analysis, clinical correlation analysis, and Lasso prognostic modeling revealed four prognostic genes closely linked to PCa outcomes. Molecular docking demonstrated strong binding affinities between these genes and the 24 PPCPs, with SRD5A2 exhibiting the highest binding affinity. Moreover, immune infiltration analysis indicated a significant correlation between SRD5A2 and the tumor immune microenvironment (TIME).

conclusionThe genes F2, SRD5A2, NEK2, and HGFAC play critical roles in PPCPs induced PCa progression, with SRD5A2 being particularly significant. These findings suggest that PPCPs may disrupt TIME homeostasis by downregulating SRD5A2 expression, thereby promoting immune evasion of PCa cells and accelerating tumor progression.