A novel capillary nano-immunoassay for assessing androgen receptor splice variant 7 in plasma. Correlation with CD133 antigen expression in circulating tumor cells. A pilot study in prostate cancer patients

Clin Transl Oncol. 2017 Nov;19(11):1350-1357. doi: 10.1007/s12094-017-1675-5. Epub 2017 Jun 9.

Abstract

Purpose: Androgen receptor (AR) splice variant 7 (AR-V7) has been related with both a higher risk of prostate cancer (PC) progression and differential responsiveness to hormonal agents versus chemotherapy. The objective of this study was to investigate the feasibility of a novel capillary nano-immunoassay in assessing AR-V7 in plasma from PC patients.

Methods: Patients with either localized or advanced PC were included in the study. Assessment of AR-V7 in plasma was performed through a capillary nano-immunoassay platform. Correlation with clinical data, stem cell biomarkers (such as CD133+), AR amplification and PTEN status was identified.

Results: The study included 72 PC patients. AR-V7 signal was detected in 21 (29%) patients: 17 (81%) had a Gleason score ≥7, 15 (71%) castration-resistant prostate cancer (CRPC), 18 (86%) metastatic disease and PSA (median) high than AR-V7 negative (p < 0.05). CD133 was expressed in 69 (96%) patients. The median CD133+ expression in circulating tumor cells CTCs was higher among the 21 AR-V7 positive cases versus AR-V7 negative (7 vs. 3). Androgen Receptor and PTEN fluorescence in situ hybridization (FISH) on CD133+ captured cells were performed: 37 cases showed ≥four CD133+ CTCs, of which 81% showed an increased AR copy number. This percentage was similar in both AR-V7-positive and AR-V7-negative patients. A total of 68% of the cases showed deletion of PTEN: 70% were ARV-7 positive vs. 67%, which were AR-V7 negative.

Conclusions: Assessing the presence of AR-V7 in plasma from PC patients is feasible by a novel capillary nano-immunoassay. AR-V7 was observed in 29% of the tumors and is more frequent in aggressive tumors.

Keywords: AR-V7; Androgen receptor; CD133; Capillary nano-immunoassay; Circulating tumor cells; PTEN.

MeSH terms

  • AC133 Antigen / metabolism*
  • Alternative Splicing*
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Follow-Up Studies
  • Humans
  • Immunoassay
  • Male
  • Nanomedicine
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Pilot Projects
  • Prognosis
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / genetics*

Substances

  • AC133 Antigen
  • AR protein, human
  • Biomarkers, Tumor
  • Receptors, Androgen