Abstract 4011: Single cell transcriptomic analysis identified a potential dormant signature in prostate cancer disseminated tumor cells

Abstract

Abstract Prostate cancer (PCa) disseminates before radical prostatectomy and can remain in the bone marrow for a prolonged period of time (>10 years) until lethal metastasis develops. These cells are referred to as disseminated tumor cells (DTC). Dormant DTC are resistant to current chemotherapy targeting cell division, therefore understanding the nature of DTC will allow the development of novel drug target to prevent overt cancer metastases. DTC were isolated from the bone marrow aspirates of PCa patients with no evidence of disease (NED, undetectable PSA level after 7-18 years after radical prostatectomy) or advanced diseases (ADV, disease progression after treatment or existing distant metastases). Eighty-five EpCAM+/CD45- individual cells were subjected to microarray gene expression analyses and two populations of cells were identified: erythroid progenitor-like and prostate epithelial cells. We utilized a dual signature method to identify EpCAM+/CD45- cells that are of prostatic origin. Comparison among prostate DTC showed that the DTC population within each patient was heterogeneous. Importantly, comparison between DTC from NED and ADV patients revealed that DTC from NED patients were enriched in a dormancy-associated signature identified in the head and neck squamous cell carcinoma, supporting the dormant nature of DTC from NED patients. Global clustering analysis and Ingenuity Pathway Analysis further identified a potential PCa dormancy signature, and this signature is significantly suppressed in a subpopulation of DTC isolated from ADV patients. We reported a single cell transcriptomic analysis to reveal for the first time clinically heterogeneous DTC population in PCa patients and a dual signature method to identify cells of prostatic origin from erythroid-progenitor cells that harbored the same epithelial (EpCAM) surface marker in the bone marrow. The proposed gene signature associated with PCa dormancy may allow development of possible biomarkers to predict prognosis and therapeutic targets to promote PCa dormancy or prevent dormancy escape. Citation Format: Hung-Ming Lam, Lisly Chéry, Ilsa Coleman, Bryce Lakely, Sandy Larson, Roger Coleman, Julio Aguirre-Ghiso, Jing Xia, Roman Gulati, Peter S. Nelson, Bruce Montgomery, Paul H. Lange, Linda A. Snyder, Robert L. Vessella, Colm Morrissey. Single cell transcriptomic analysis identified a potential dormant signature in prostate cancer disseminated tumor cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4011. doi:10.1158/1538-7445.AM2014-4011