Abstract | PURPOSE: Most prostate cancer mortality can be attributed to metastatic castration resistant prostate cancer, an advanced stage that remains incurable despite recent advances. The AR ( androgen receptor) signaling axis remains active in castration resistant prostate cancer. Recent studies suggest that expression of the AR-V (AR splice variant) AR-V7 may underlie resistance to abiraterone and enzalutamide. However, controversy exists over the optimal assay. Our objective was to develop a fast and sensitive assay for AR-Vs in patients. MATERIALS AND METHODS: Two approaches were assessed in this study. The first approach was based on depletion of leukocytes and the second one used RNA purified directly from whole blood preserved in PAXgene® tubes. Transcript expression was analyzed by quantitative reverse transcription-polymerase chain reaction. RESULTS: Through a side-by-side comparison we found that the whole blood approach was suitable to detect AR-Vs. The specificity of the assay was corroborated in a cancer-free cohort. Using the PAXgene assay samples from a cohort of 46 patients with castration resistant prostate cancer were analyzed. Overall, AR-V7 and ARv567es were detected in 67.53% and 29.87% of samples, respectively. Statistical analysis revealed a strong association of AR-V positivity with a history of second line hormonal therapies. CONCLUSIONS: To our knowledge this is the first study to demonstrate that PAXgene preserved whole blood can be used to obtain clinically relevant information regarding the expression of 2 AR-Vs. These data on a castration resistant prostate cancer cohort support a role for AR-Vs in resistance to therapies targeting the AR ligand-binding domain.
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Authors | Xichun Liu, Elisa Ledet, Dongying Li, Ary Dotiwala, Allie Steinberger, Allison Feibus, Jianzhuo Li, Yanfeng Qi, Jonathan Silberstein, Benjamin Lee, Yan Dong, Oliver Sartor, Haitao Zhang |
Journal | The Journal of urology
(J Urol)
Vol. 196
Issue 6
Pg. 1758-1763
(12 2016)
ISSN: 1527-3792 [Electronic] United States |
PMID | 27449259
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- AR protein, human
- Protein Isoforms
- Receptors, Androgen
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Topics |
- Adult
- Aged
- Cross-Sectional Studies
- Humans
- Male
- Middle Aged
- Prostatic Neoplasms
(blood)
- Prostatic Neoplasms, Castration-Resistant
(blood, diagnosis)
- Protein Isoforms
(blood)
- Receptors, Androgen
(blood)
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