Monocyte differentiation dynamics and ligand-receptor interactions in peripheral blood of patients with prostate cancer and BPH: a comparative scRNA-seq analysis

Monocytes critically shape immune responses in prostate diseases, yet their differentiation dynamics in prostate cancer (PCa) versus benign prostatic hyperplasia (BPH) remain unclear. We employed single-cell RNA sequencing to analyze peripheral blood mononuclear cells from four PCa patients (Gleason 3+3 to 3+4, stages T2N0M0–T3bN0M0) and three BPH patients. Unsupervised clustering identified 16 distinct cell populations, emphasizing classical (CD14++CD16−), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) monocyte subsets. PCa samples showed greater monocyte heterogeneity with seven classical subsets versus six in BPH, reflecting increased malignant plasticity. Transcriptionally, PCa monocytes upregulated oncogenic MALAT1, metastasis-associated S100A8/S100A9 and VCAN, and immunosuppressive CD14/CD36, supporting angiogenesis and tumor growth. Conversely, BPH monocytes maintained protective functions through ALDH1A2, anti-proliferative ZFP36, and tissue homeostasis regulators TMEM176B, USP30-AS1, and TCOF1. Ligand–receptor analysis distinguished disease contexts: PCa monocytes formed restricted networks dominated by ANXA1–FPR1 and TGFβ1 signaling, fostering immunosuppression. BPH exhibited broader networks integrating pro-inflammatory chemokines (CCL3/CCL5–CCR1) and metabolic NAMPT–BSG pathways, consistent with controlled inflammation and repair. Our findings define distinct molecular programs of circulating monocytes in malignant versus benign prostate disease, providing potential biomarkers for differential diagnosis and immunomodulatory therapy targets.