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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords:

• Benign prostate hyperplasia
• castration-resistant prostate cancer
• WGCNA
• single-cell RNA sequencing
• immune microenvironment

Acknowledgments

This work benefited from open source of public databases. We appreciated the efforts made by the researchers and staffs to expand and improve the databases.

Ethical approval

Ethical approval was waived by the institutional ethics committee because data are obtained from public databases, and all the patients are de-identified.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The original contributions presented in the study are included in the article/Supplementary Table S1, further inquiries can be directed to the corresponding author. All the scripts used in this study could be obtained by request to the corresponding author.

Additional information

Funding

This project was supported by the Clinical Medicine Innovation Program of Jinan City [202019125], Shandong Provincial Nature Science Foundation [ZR2020QH240], the National Nature Science Foundation of China [NSFC82002719], the China Postdoctoral Science Foundation [2022M711977], and Cultivating Funding of Shandong Provincial Qianfoshan Hospital [QYPY2019NSFC1005].