Integrative exploration of the mutual gene signatures and immune microenvironment between benign prostate hyperplasia and castration-resistant prostate cancer

Fei Wu, Hao Ning, Yang Sun, Haihu Wu, Jiaju Lyu

Benign prostate hyperplasia (BPH) and prostate cancer (CaP) are among the most frequently occurring prostatic diseases. When CaP progressed to castration-resistant CaP (CRPC), the prognosis is poor. Although CaP/CRPC and BPH frequently coexist in prostate, the inter-relational mechanism between them is largely unknown. Single-cell RNA sequencing, bulk-RNA sequencing, and microarray data of BPH, CaP in the Gene Expression Omnibus database were obtained and comprehensively analyzed. Weighted Gene Co-Expression Network Analysis (WGCNA) and lasso regression analysis were performed to explore the potential biomarkers. With WGCNA, five modules in BPH, two in CaP, and three in CRPC were identified as significant modules. Pathway enrichment analysis found that the epigenetics and chromosomal-related signaling were dominantly clustered in the CaP group but not in BPH and CRPC. Lasso regression analysis was used to analyze further the mutual genes between the BPH module and the CRPC module. As a result, DDA1, ERG28, OGFOD1, and OXA1L were significantly correlated with the transcriptomic features in both BPH and CRPC. More importantly, the role of the four gene signatures was validated in two independent anti-PD-1 immunotherapy cohort. This study revealed the shared gene signatures and immune microenvironment between BPH and CRPC. The identified hub genes, including DDA1, ERG28, OGFOD1, and OXA1L, might be potential therapeutic targets for facilitating immunotherapy in prostate cancer.