Single cell analysis reveals onset of multiple progression associated transcriptomic remodellings in prostate cancer

Dissecting heterogeneity of prostate tumors is a clinical imperative. Here, we analyzed the transcriptomes of 36,424 single-cells from 13 prostate tumors, and identified lineage specific epithelial cells underlying disease aggressiveness. Activation of various progression-associated transcriptomic programs exists in the tumor microenvironment (TME). Notably, we observed promiscuous KLK3 expression in TME and validated the ability of tumor-derived exosomes in altering T cell transcriptomes. Single-cell profiling of a high-risk patient tumor and lymph nodes provided evidence that KLK3 ectopic expression is associated with micrometastases. Close cell-cell communication exists among tumor and TME cells. We identified an endothelial subset harboring active communication (aEC) with tumor cells. Together with sequencing of an additional 11 samples, we showed that aECs are enriched in castration-resistant prostate cancer and promote cancer cell invasion. Finally, we created a user-friendly web interface (www.pradcellatlas.com) for the sequenced data as a resource for the research community. The 13 prostate tumor samples used in this study were collected from patients who had undergone radical prostatectomy at Shanghai Changhai Hospital. Single cell RNA sequencing was performed with 10XGenomics. >>>Submitter states that raw data are not available due to patient privacy concerns<<<