Transcriptomic Heterogeneity of Androgen Receptor Activity Defines a
Publication/Presentation Date
11-15-2019
Abstract
PURPOSE: The heterogeneity of androgen receptor (AR)-activity (AR-A) is well-characterized in heavily treated metastatic castration-resistant prostate cancer (mCRPC). However, the diversity and clinical implications of AR-A in treatment-naïve primary prostate cancer is largely unknown. We sought to characterize AR-A in localized prostate cancer and understand its molecular and clinical implications.
EXPERIMENTAL DESIGN: Genome-wide expression profiles from prostatectomy or biopsy samples from 19,470 patients were used, all with independent pathology review. This was comprised of prospective discovery (
RESULTS: A low AR-active subclass was identified, which comprised 9%-11% of each cohort, and was characterized by increased immune signaling, neuroendocrine expression, and decreased DNA repair. These tumors were predominantly
CONCLUSIONS: Leveraging large-scale transcriptomic data allowed the identification of an aggressive subtype of treatment-naïve primary prostate cancer that harbors molecular features more analogous to mCRPC. This suggests that a preexisting subgroup of patients may have tumors that are predisposed to fail multiple current standard-of-care therapies and warrant dedicated therapeutic investigation.
Volume
25
Issue
22
First Page
6721
Last Page
6730
ISSN
1557-3265
Published In/Presented At
Spratt, D. E., Alshalalfa, M., Fishbane, N., Weiner, A. B., Mehra, R., Mahal, B. A., Lehrer, J., Liu, Y., Zhao, S. G., Speers, C., Morgan, T. M., Dicker, A. P., Freedland, S. J., Karnes, R. J., Weinmann, S., Davicioni, E., Ross, A. E., Den, R. B., Nguyen, P. L., Feng, F. Y., … Schaeffer, E. M. (2019). Transcriptomic Heterogeneity of Androgen Receptor Activity Defines a de novo low AR-Active Subclass in Treatment Naïve Primary Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 25(22), 6721–6730. https://doi.org/10.1158/1078-0432.CCR-19-1587
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
31515456
Department(s)
Administration and Leadership
Document Type
Article