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Int J Mol Sci. 2016 Aug 4;17(8). pii: E1264. doi: 10.3390/ijms17081264.

Droplet Digital PCR Based Androgen Receptor Variant 7 (AR-V7) Detection from Prostate Cancer Patient Blood Biopsies.

Ma Y1, Luk A2, Young FP3,4, Lynch D5,6, Chua W7, Balakrishnar B8, de Souza P9,10,11,12, Becker TM13,14,15.

Author information

1
Centre for Circulating Tumor Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St., Liverpool, NSW 2170, Australia. yafeng.ma@unsw.edu.au.
2
Centre for Circulating Tumor Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St., Liverpool, NSW 2170, Australia. alison.luk@unsw.edu.au.
3
Centre for Circulating Tumor Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St., Liverpool, NSW 2170, Australia. francis.young@student.unsw.edu.au.
4
South Western Clinical School, University of New South Wales, Goulburn St., Liverpool, NSW 2170, Australia. francis.young@student.unsw.edu.au.
5
Centre for Circulating Tumor Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St., Liverpool, NSW 2170, Australia. 18292682@student.westernsydney.edu.au.
6
Western Sydney University Clinical School, Elizabeth St., Liverpool, NSW 2170, Australia. 18292682@student.westernsydney.edu.au.
7
Department of Medical Oncology, Liverpool Hospital, Elizabeth St & Goulburn St., Liverpool, NSW 2170, Australia. Wei.Chua2@sswahs.nsw.gov.au.
8
Department of Medical Oncology, Liverpool Hospital, Elizabeth St & Goulburn St., Liverpool, NSW 2170, Australia. Bavanthi.Balakrishna@sswahs.nsw.gov.au.
9
Centre for Circulating Tumor Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St., Liverpool, NSW 2170, Australia. P.DeSouza@westernsydney.edu.au.
10
South Western Clinical School, University of New South Wales, Goulburn St., Liverpool, NSW 2170, Australia. P.DeSouza@westernsydney.edu.au.
11
Western Sydney University Clinical School, Elizabeth St., Liverpool, NSW 2170, Australia. P.DeSouza@westernsydney.edu.au.
12
Department of Medical Oncology, Liverpool Hospital, Elizabeth St & Goulburn St., Liverpool, NSW 2170, Australia. P.DeSouza@westernsydney.edu.au.
13
Centre for Circulating Tumor Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, 1 Campbell St., Liverpool, NSW 2170, Australia. t.becker@unsw.edu.au.
14
South Western Clinical School, University of New South Wales, Goulburn St., Liverpool, NSW 2170, Australia. t.becker@unsw.edu.au.
15
Western Sydney University Clinical School, Elizabeth St., Liverpool, NSW 2170, Australia. t.becker@unsw.edu.au.

Abstract

Androgen receptor splice variant V7 (AR-V7) was recently identified as a valuable predictive biomarker in metastatic castrate-resistant prostate cancer. Here, we report a new, sensitive and accurate screen for AR-V7 mRNA expression directly from circulating tumor cells (CTCs): We combined EpCAM-based immunomagnetic CTC isolation using the IsoFlux microfluidic platform with droplet digital polymerase chain reaction (ddPCR) to analyze total AR and AR-V7 expression from prostate cancer patients CTCs. We demonstrate that AR-V7 is reliably detectable in enriched CTC samples with as little as five CTCs, even considering tumor heterogeneity, and confirm detection of AR-V7 in CTC samples from advanced prostate cancer (PCa) patients with AR-V7 detection limited to castrate resistant disease status in our sample set. Sensitive molecular analyses of circulating tumor cells (CTCs) or circulating tumor nucleic acids present exciting strategies to detect biomarkers, such as AR-V7 from non-invasive blood samples, so-called blood biopsies.

KEYWORDS:

AR-V7; CTC; androgen receptor; biomarker; ddPCR; prostate cancer

PMID:
27527157
PMCID:
PMC5000662
DOI:
10.3390/ijms17081264
[Indexed for MEDLINE]
Free PMC Article

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