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Co-expression and clinical utility of AR-FL and AR splice variants AR-V3, AR-V7 and AR-V9 in prostate cancer

Biomarker research, 2023-04, Vol.11 (1), p.37-37, Article 37 [Peer Reviewed Journal]

2023. The Author(s). ;COPYRIGHT 2023 BioMed Central Ltd. ;2023. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;The Author(s) 2023 ;ISSN: 2050-7771 ;EISSN: 2050-7771 ;DOI: 10.1186/s40364-023-00481-w ;PMID: 37016463

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  • Title:
    Co-expression and clinical utility of AR-FL and AR splice variants AR-V3, AR-V7 and AR-V9 in prostate cancer
  • Author: Wüstmann, Neele ; Seitzer, Konstantin ; Humberg, Verena ; Vieler, Julia ; Grundmann, Norbert ; Steinestel, Julie ; Tiedje, Dorothee ; Duensing, Stefan ; Krabbe, Laura-Maria ; Bögemann, Martin ; Schrader, Andres Jan ; Bernemann, Christof ; Schlack, Katrin
  • Subjects: Alternative splicing ; Androgen receptor ; Androgen receptor splice variants ; Androgen receptor targeted agents ; Androgen receptors ; Biomarker ; Biomarkers ; Biopsy ; Cancer therapies ; Circulating tumor cells ; CRISPR ; Development and progression ; Disease ; Gene expression ; Liquid biopsy ; Lymphocytes ; Messenger RNA ; Metastases ; Metastasis ; mRNA ; Multivariate analysis ; Patients ; Prostate cancer ; Scientific equipment and supplies industry
  • Is Part Of: Biomarker research, 2023-04, Vol.11 (1), p.37-37, Article 37
  • Description: Androgen receptor (AR) splice variants (AR-Vs) have been discussed as a biomarker in prostate cancer (PC). However, some reports question the predictive property of AR-Vs. From a mechanistic perspective, the connection between AR full length (AR-FL) and AR-Vs is not fully understood. Here, we aimed to investigate the dependence of AR-FL and AR-V expression levels on AR gene activity. Additionally, we intended to comprehensively analyze presence of AR-FL and three clinically relevant AR-Vs (AR-V3, AR-V7 and AR-V9) in different stages of disease, especially with respect to clinical utility in PC patients undergoing AR targeted agent (ARTA) treatment. AR-FL and AR-V levels were analyzed in PC and non-PC cell lines upon artificial increase of AR pre-mRNA using either drug treatment or AR gene activation. Furthermore, expression of AR-FL and AR-Vs was determined in PC specimen at distinct stages of disease (primary (n = 10) and metastatic tissues (n = 20), liquid biopsy samples (n = 422), mCRPC liquid biopsy samples of n = 96 patients starting novel treatment). Finally, baseline AR-FL and AR-V status was correlated with clinical outcome in a defined cohort of n = 65 mCRPC patients undergoing ARTA treatment. We revealed rising levels of AR-FL accompanied with appearance and increase of AR-Vs in dependence of elevated AR pre-mRNA levels. We also noticed increase in AR-FL and AR-V levels throughout disease progression. AR-V expression was always associated with high AR-FL levels without any sample being solely AR-V positive. In patients undergoing ARTA treatment, AR-FL did show prognostic, yet not predictive validity. Additionally, we observed a substantial clinical response to ARTA treatment even in AR-V positive patients. Accordingly, multivariate analysis did not demonstrate independent significance of AR-Vs in neither predictive nor prognostic clinical utility. We demonstrate a correlation between AR-FL and AR-V expression during PC progression; with AR-V expression being a side-effect of elevated AR pre-mRNA levels. Clinically, AR-V positivity relies on high levels of AR-FL, making cells still vulnerable to ARTA treatment, as demonstrated by AR-FL and AR-V positive patients responding to ARTA treatment. Thus, AR-FL and AR-V might be considered as a prognostic, yet not predictive biomarker in mCRPC patients.
  • Publisher: England: BioMed Central Ltd
  • Language: English
  • Identifier: ISSN: 2050-7771
    EISSN: 2050-7771
    DOI: 10.1186/s40364-023-00481-w
    PMID: 37016463
  • Source: PubMed Central
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    ProQuest Central
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