Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states

Methods: To characterize the prostate cancer tumor microenvironment, we performed single-cell RNA-sequencing on prostate biopsies, prostatectomy specimens, and patient-derived organoids from localized prostate cancer patients. Results: We identify a population of tumor-associated club cells that could be associated with prostate carcinogenesis and uncover heterogeneous cellular states in prostate epithelial cells marked by high androgen signaling states that are enriched in prostate cancer. ERG- tumor cells, compared to ERG+ cells, demonstrate shared heterogeneity with surrounding luminal epithelial cells and appear to give rise to common tumor microenvironment responses. Finally, we show that prostate epithelial organoids recapitulate tumor-associated epithelial cell states and are enriched with distinct cell types and states from their parent tissues. Conclusions:Our results provide diagnostically relevant insights and advance our understanding of the cellular states associated with prostate carcinogenesis. Single-cell RNA sequencing based on Seq-Well S^3 protocol of 6 prostate biopsies from 3 different patients, 4 radical prostatectomies with tumor-only samples from 4 patients, and 4 radical prostatectomies with matched normal samples from 4 patients. Organoids derived from radical prostatectomy paired tumor and normal tissue samples.