Genes Associated with Bicalutamide and Zoladex Effects in Benign Prostatic Hyperplasia via Transcriptomic and Network Pharmacology Analyses

Existing research indicates that bicalutamide and zoladex hold considerable promise in the treatment of prostate cancer. Nonetheless, their precise roles in the management of benign prostatic hyperplasia (BPH) remain inadequately elucidated. This study sought to identify and validate key genes associated with the effects of bicalutamide and zoladex in BPH, with the potential to inform the development of targeted therapeutic strategies for this condition. Datasets on benign prostatic hyperplasia (BPH) were obtained from publicly accessible databases. Initially, intersection genes were identified by overlapping the results of differential expression analysis (comparing BPH to control) with the target genes of bicalutamide and Zoladex, which were retrieved through database searches. Subsequently, key genes were identified using protein-protein interaction (PPI) networks, machine learning algorithms, and gene expression analyses. Functional enrichment and molecular docking analyses were then performed to investigate the biological mechanisms associated with these key genes. Finally, immunohistochemical (IHC) analysis was conducted on clinical samples to validate the expression levels of the key genes. In this study, NQO1, CLPP, HMGCR, and SORD were identified as pivotal genes associated with BPH, all demonstrating significantly reduced expression levels in BPH samples. Importantly, these genes were prominently co-enriched within the "oxidative phosphorylation" pathway. Additionally, CLPP, HMGCR, and NQO1 exhibited strong binding affinities with the pharmaceutical agents bicalutamide and zoladex. Specifically, the interaction between NQO1 and bicalutamide yielded a binding energy of -10.8 kcal/mol, whereas the binding energy between NQO1 and zoladex was − 38.05 kcal/mol. Immunohistochemistry (IHC) analysis further revealed that the expression levels of NQO1, CLPP, HMGCR, and SORD were significantly elevated in the post-medication group compared to the pre-medication group. This study highlights NQO1, CLPP, HMGCR, and SORD as potential therapeutic targets for BPH, providing mechanistic insights into bicalutamide and Zoladex efficacy.