Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

AR-V7 Positivity Varies with Circulating Tumor Cell (CTC) Enrichment and Novel CTC Enrichment Is Able to Reduce AR-V7 False Positivity

Takehiko Nakasato
* ORCID logo ,
Chiho Kusaka
,
Mika Ota
,
Yuki Hasebe
,
Kumiko Ueda
,
Tsutomu Unoki
,
Kazuhiko Oshinomi
,
Jun Morita
,
Yoshiko Maeda
,
Takeshi Shichijo
,
Michio Naoe
,
Yoshio Ogawa
Version 1 : Received: 19 February 2020 / Approved: 20 February 2020 / Online: 20 February 2020 (06:45:47 CET)

A peer-reviewed article of this Preprint also exists.

Nakasato, T.; Kusaka, C.; Ota, M.; Hasebe, Y.; Ueda, K.; Unoki, T.; Oshinomi, K.; Morita, J.; Maeda, Y.; Shichijo, T.; Naoe, M.; Ogawa, Y. A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer. Diagnostics 2020, 10, 151. Nakasato, T.; Kusaka, C.; Ota, M.; Hasebe, Y.; Ueda, K.; Unoki, T.; Oshinomi, K.; Morita, J.; Maeda, Y.; Shichijo, T.; Naoe, M.; Ogawa, Y. A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer. Diagnostics 2020, 10, 151.

Abstract

Background: The AR-V7 splice variant is a cause of castration-resistant prostate cancer (CRPC). However, testing for the presence of AR-V7 by RT-PCR shows AR-V7 positivity in healthy individuals. We hypothesized that the positivity reflected contamination by hematopoietic cells. We tried a novel CTC enrichment instrument using Celsee® to clear hematopoietic cells. Methods: We tested whole blood or Celsee-enriched samples for AR-V7 by RT-PCR and included samples from 41 CRPC patients undergoing sequential therapy. We evaluated the associations between AR-V7 status and clinical factors. We evaluated factors affecting AR-V7 positivity. Results: AR-V7 positivity was lower in Celsee-enriched than in whole blood specimens. AR-V7 and clinical factors did not predict the therapy effectiveness. We found no significant differences in the effectiveness of Enz/Abi upon AR-V7 evaluation. All AR-V7 positive patients had resistance to Enz/Abi. DTX, CBZ, and Radium223 treatment showed no significant difference in the treatment effectiveness, regardless of AR-V7 presence. AR-V7 was more frequently positive than EOD2 in cases with bone metastases. Conclusion: Celsee® CTC enrichment suppresses the AR-V7 false positivity. All AR-V7 positive patients presented resistance to Enz/Abi. DTX, CBZ, and Radium223 were effective and remained treatment options. AR-V7 positivity should progressively appear in patients with advanced bone metastases.

Keywords

AR-V7; Androgen receptors; Docetaxel; Cabazitaxel; Abiraterone; Enzalutamide

Subject

Medicine and Pharmacology, Urology and Nephrology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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