Androgen receptor variant shows heterogeneous expression in prostate cancer according to differentiation stage.

TitleAndrogen receptor variant shows heterogeneous expression in prostate cancer according to differentiation stage.
Publication TypeJournal Article
Year of Publication2021
AuthorsGjyrezi A, Galletti G, Zhang J, Worroll D, Sigouros M, Kim S, Cooley V, Ballman KV, Ocean AJ, Shah MA, Scandura JM, Sboner A, Nanus DM, Beltran H, Tagawa S, Giannakakou P
JournalCommun Biol
Date Published2021 06 24
KeywordsCell Line, Tumor, Humans, Male, Neoplasm Staging, Neoplastic Cells, Circulating, Prostatic Neoplasms, Receptors, Androgen, RNA-Seq

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 (NanoString) 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.

Alternate JournalCommun Biol
PubMed ID34168263
PubMed Central IDPMC8225618
Grant ListR01 CA179100 / CA / NCI NIH HHS / United States
R21 CA216800 / CA / NCI NIH HHS / United States
T32 CA062948 / CA / NCI NIH HHS / United States
Related Faculty: 
Andrea Sboner, Ph.D.

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