Single-Cell Profiling of Mononuclear Cells Identifies Transcriptomics Signatures Differentiating Prostate Cancer From Benign Prostatic Hyperplasia

Abstract

Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) share overlapping etiological factors but differ molecularly. In the study, 4 patients with prostate cancer and 3 patients with BPH were included. All patients with prostate cancer and BPH had a histologically confirmed diagnosis. Among the prostate cancer group were 3 patients with acinar prostate adenocarcinoma and 1 patient with small-acinar prostate adenocarcinoma. Using single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from PCa and BPH patients, we identified 16 immune cell clusters, with elevated CD14+ monocytes, NK cells, and γδ T cells in PCa. Differential gene expression analysis revealed 40 overexpressed genes in PCa monocytes, including CSMD1, ZBTB16, ZNF217, and SERPINI2, linked to tumor progression, cell cycle regulation, EMT, androgen signaling, and metabolism. SCN2A was highly expressed in PCa B cells, while ABO, FMN1, and TXNIP in CD4+ T cells modulated immune evasion, cytoskeletal regulation, and oxidative stress. Pathway analysis showed PCa monocytes had heightened interleukin-27 signaling, whereas BPH monocytes exhibited increased cholesterol storage and Notch signaling. CellChat analysis highlighted monocytes' central role in immune regulation, with distinct interactions via MIF, galectin, and TGF-β pathways in PCa and BPH. These findings reveal unique immune microenvironments and transcriptional heterogeneity between PCa and BPH, offering potential biomarkers for differentiation and insights into prostate pathology mechanisms.