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A Whole Blood Assay for AR-V7 and AR v567es in Patients with Prostate Cancer

2016; Lippincott Williams & Wilkins; Volume: 196; Issue: 6 Linguagem: Inglês

10.1016/j.juro.2016.06.095

1527-3792

Xichun Liu, Elisa M. Ledet, Dongying Li, Ary Dotiwala, Allie E. Steinberger, Allison H. Feibus, Jianzhuo Li, Yanfeng Qi, Jonathan Silberstein, Benjamin Lee, Yan Dong, Oliver Sartor, Haitao Zhang,

Urologic and reproductive health conditions

No AccessJournal of UrologyInvestigative Urology1 Dec 2016A Whole Blood Assay for AR-V7 and ARv567es in Patients with Prostate Cancer Xichun Liu, Elisa Ledet, Dongying Li, Ary Dotiwala, Allie Steinberger, Allison Feibus, Jianzhuo Li, Yanfeng Qi, Jonathan Silberstein, Benjamin Lee, Yan Dong, Oliver Sartor, and Haitao Zhang Xichun LiuXichun Liu Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana Equal study contribution. More articles by this author , Elisa LedetElisa Ledet Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana Equal study contribution. More articles by this author , Dongying LiDongying Li Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author , Ary DotiwalaAry Dotiwala Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author , Allie SteinbergerAllie Steinberger Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author , Allison FeibusAllison Feibus Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author , Jianzhuo LiJianzhuo Li Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author , Yanfeng QiYanfeng Qi Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author , Jonathan SilbersteinJonathan Silberstein Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author , Benjamin LeeBenjamin Lee Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author , Yan DongYan Dong Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author , Oliver SartorOliver Sartor Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author , and Haitao ZhangHaitao Zhang Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.06.095AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail 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. References 1 : Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res2008; 68: 5469. Google Scholar 2 : Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res2009; 69: 16. 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Google Scholar © 2016 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byStuopelyte K, Sabaliauskaite R, Bakavicius A, Haflidadóttir B, Visakorpi T, Väänänen R, Patel C, Danila D, Lilja H, Lazutka J, Ulys A, Jankevicius F and Jarmalaite S (2020) Analysis of AR-FL and AR-V1 in Whole Blood of Patients with Castration Resistant Prostate Cancer as a Tool for Predicting Response to Abiraterone AcetateJournal of Urology, VOL. 204, NO. 1, (71-78), Online publication date: 1-Jul-2020.Atala A (2017) Re: Activation of Notch1 Synergizes with Multiple Pathways in Promoting Castration-Resistant Prostate CancerJournal of Urology, VOL. 197, NO. 6, (1458-1459), Online publication date: 1-Jun-2017.Antonarakis E and Luo J (2016) Blood Based Detection of Androgen Receptor Splice Variants in Patients with Advanced Prostate CancerJournal of Urology, VOL. 196, NO. 6, (1606-1607), Online publication date: 1-Dec-2016. Volume 196Issue 6December 2016Page: 1758-1763Supplementary Materials Advertisement Copyright & Permissions© 2016 by American Urological Association Education and Research, Inc.Keywordsreceptorsandrogenbloodbiomarkerstumorprotein isoformsprostatic neoplasmsMetricsAuthor Information Xichun Liu Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana Equal study contribution. More articles by this author Elisa Ledet Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana Equal study contribution. More articles by this author Dongying Li Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author Ary Dotiwala Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author Allie Steinberger Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author Allison Feibus Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author Jianzhuo Li Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author Yanfeng Qi Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author Jonathan Silberstein Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author Benjamin Lee Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author Yan Dong Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author Oliver Sartor Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author Haitao Zhang Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana More articles by this author Expand All Advertisement PDF downloadLoading ...