title: Droplet Digital PCR Based Androgen Receptor Variant 7 (AR-V7) Detection from Prostate Cancer Patient Blood Biopsies.
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.
authors.affiliation: 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.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Alison
authors.initials: A
authors.lastname: Luk
authors.affiliation: 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.|South Western Clinical School, University of New South Wales, Goulburn St., Liverpool, NSW 2170, Australia. francis.young@student.unsw.edu.au.
authors.forename: Francis P
authors.initials: FP
authors.lastname: Young
authors.affiliation: 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.|Western Sydney University Clinical School, Elizabeth St., Liverpool, NSW 2170, Australia. 18292682@student.westernsydney.edu.au.
authors.forename: David
authors.initials: D
authors.lastname: Lynch
authors.affiliation: Department of Medical Oncology, Liverpool Hospital, Elizabeth St & Goulburn St., Liverpool, NSW 2170, Australia. Wei.Chua2@sswahs.nsw.gov.au.
authors.forename: Wei
authors.initials: W
authors.lastname: Chua
authors.affiliation: Department of Medical Oncology, Liverpool Hospital, Elizabeth St & Goulburn St., Liverpool, NSW 2170, Australia. Bavanthi.Balakrishna@sswahs.nsw.gov.au.
authors.forename: Bavanthi
authors.initials: B
authors.lastname: Balakrishnar
authors.affiliation: 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.|South Western Clinical School, University of New South Wales, Goulburn St., Liverpool, NSW 2170, Australia. P.DeSouza@westernsydney.edu.au.|Western Sydney University Clinical School, Elizabeth St., Liverpool, NSW 2170, Australia. P.DeSouza@westernsydney.edu.au.|Department of Medical Oncology, Liverpool Hospital, Elizabeth St & Goulburn St., Liverpool, NSW 2170, Australia. P.DeSouza@westernsydney.edu.au.
authors.forename: Paul
authors.initials: P
authors.lastname: de Souza
authors.affiliation: 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.|South Western Clinical School, University of New South Wales, Goulburn St., Liverpool, NSW 2170, Australia. t.becker@unsw.edu.au.|Western Sydney University Clinical School, Elizabeth St., Liverpool, NSW 2170, Australia. t.becker@unsw.edu.au.
authors.forename: Therese M
authors.initials: TM
authors.lastname: Becker
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D045744:Cell Line, Tumor; D000071858:Epithelial Cell Adhesion Molecule / Q000032:analysis; D006801:Humans; D008297:Male; D044085:Microfluidics / Q000379:methods*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D016133:Polymerase Chain Reaction / Q000379:methods*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000097:blood* / Q000235:genetics; D012680:Sensitivity and Specificity
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D012333:RNA, Messenger; D011944:Receptors, Androgen
keywords: AR-V7; CTC; androgen receptor; biomarker; ddPCR; prostate cancer