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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

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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.

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Authors and Affiliations

  1. Institute of Biomedical Research of Salamanca (IBSAL), Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain

    J. L. García, I. Misiewicz-Krzeminska & P. Krzeminski

  2. Medical Oncology Service, Hospital Universitario de Salamanca Institute of Biomedical Research of Salamanca (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain

    R. Lozano, J. Fernández-Mateos, S. Alfonso, R. García & J. J. Cruz-Hernández

  3. Dpto. de Oncología Médica, Complejo Asistencial Nuestra Señora de Sonsoles, Av.Juan Carlos I, s/n, 05071, Ávila, Spain

    R. A. Marcos

  4. Urology Department, Hospital Universitario de Salamanca Grupo de Investigación Traslacional de Urología (GITUR), Institute of Biomedical Research of Salamanca (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain

    F. Gómez-Veiga, Á. Virseda & M. Herrero

  5. Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro, 3, 28029, Madrid, Spain

    D. Olmos

  6. Medical Oncology Department, CNIO-IBIMA Genitourinary Cancer Clinical Research Unit, Hospital Universitario Virgen de la Victoria y Regional de Málaga, Campus de Teatinos S/N, 29010, Málaga, Spain

    D. Olmos

Authors
  1. J. L. García
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  2. R. Lozano
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  3. I. Misiewicz-Krzeminska
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  4. J. Fernández-Mateos
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  6. S. Alfonso
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  7. R. A. Marcos
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  8. R. García
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  9. F. Gómez-Veiga
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  10. Á. Virseda
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  11. M. Herrero
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  13. J. J. Cruz-Hernández
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Corresponding authors

Correspondence to J. L. García or J. J. Cruz-Hernández.

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Conflict to interest

We declare that we have no conflict of interest.

Funding

Partiality supported by Grant from Gerencia Regional de Salud, Junta de Castilla y León (Refs: GRS 992/A/14 y BIO/SA35/14) and INNOCAMPUS Program (CEI10-1-0010). We thank M.A. Hernández from the IBSAL for their excellent technical assistance.

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García, J.L., Lozano, R., Misiewicz-Krzeminska, I. et al. 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 19, 1350–1357 (2017). https://doi.org/10.1007/s12094-017-1675-5

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  • DOI: https://doi.org/10.1007/s12094-017-1675-5

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