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

By Hanbing Song, Hannah N.W. Weinstein, Paul Allegakoen, Marc H Wadsworth, Jamie Xie, Heiko Yang, Felix Y Feng, Peter R Carroll, Bruce Wang, Matthew R. Cooperberg, Alex K Shalek, Franklin W. Huang

Posted 08 Nov 2020
bioRxiv DOI: 10.1101/2020.11.06.359802

Prostate cancer is the second most common malignancy in men worldwide and consists of a mixture of tumor and non-tumor cell types. 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. We identify a population of tumor-associated club cells that may act as progenitor cells 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. Our results provide diagnostically relevant insights and advance our understanding of the cellular states associated with prostate carcinogenesis. ### Competing Interest Statement A.K.S. reports compensation for consulting and/or SAB membership from Merck, Honeycomb Biotechnologies, Cellarity, Repertoire Immune Medicines, Orche Bio, and Dahlia Biosciences. F.Y.F. reports compensation for consulting and/or SAB membership from Astellas, Bayer, Blue Earth Diagnostics, Celgene, Genentech, Janssen Oncology, Myovant, Roivant, Sanofi, PFS Genomics, and SerImmune.

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