Androgen receptor variant shows heterogeneous expression in prostate cancer according to differentiation stage
Abstract
Quantitation of androgen receptor variant (AR-V) expression in circulating tumor cells (CTCs) from patients with metastatic castration-resistant prostate cancer (mCRPC) has great potential for treatment customization. However, the absence of a uniform CTC isolation platform and consensus on an analytical assay has prevented the incorporation of these measurements in routine clinical practice. Here, we present a single-CTC sensitive digital droplet PCR (ddPCR) assay for the quantitation of the two most common AR-Vs, AR-V7, and AR-v567es, using antigen agnostic CTC enrichment. In a cohort of 29 mCRPC patients, we identify AR-V7 in 66% and AR-v567es in 52% of patients. These results are corroborated using another gene expression platform (NanoStringTM) and by analysis of RNA-Seq data from patients with mCRPC (SU2C- PCF Dream Team). We next quantify AR-V expression in matching EpCAM-positive vs EpCAM-negative CTCs, as EpCAM-based CTC enrichment is commonly used. We identify lower AR-V prevalence in the EpCAM-positive fraction, suggesting that EpCAM-based CTC enrichment likely underestimates AR-V prevalence. Lastly, using single CTC analysis we identify enrichment for AR-v567es in patients with neuroendocrine prostate cancer (NEPC) indicating that AR-v567es may be involved in lineage plasticity, which warrants further mechanistic interrogation.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 24, 2021
- Source ID
- 10.1038/s42003-021-02321-9
Entities
People
- Ada Gjyrezi
- Allyson J. Ocean
- Andrea Sboner
- Daniel Worroll
- David M. Nanus
- Giuseppe Galletti
- Himisha Beltran
- Jiaren Zhang
- Joseph M. Scandura
- Karla V. Ballman
- Manish A Shah
- Michael Sigouros
- Paraskevi Giannakakou
- Scott T Tagawa
- Seaho Kim
- Victoria Cooley
Organizations
- United States Department of Defense