Prognostic role of Androgen Receptor splice variant 7 (AR-V7) in the pathogenesis of breast cancer.

Background: The Androgen Receptor (AR) has emerged as an endocrine therapy target in Breast Cancer, exhibiting up to 80% expression in clinical cases. AR-V7, a constitutively activated splice variant of AR with a truncated ligand-binding domain (LBD), demonstrates ligand-independent transcriptional activity and resistance to nonsteroidal antiandrogens like Bicalutamide or Enzalutamide, targeting the LBD. In metastatic prostate cancer, elevated AR-V7 levels lead to therapeutic resistance and increased metastasis.
Methods: In this study, we evaluated the expression of AR and AR-V7 in cell lines and a cohort of 89 patients undergoing surgical intervention for treatment-naïve breast cancer. Further clinicopathological correlations and survival analysis were performed to evaluate the relationship between the AR and AR-V7 expression and clinical outcomes.
Results: AR-V7/AR-FL ratio was elevated in the TNBC cell line and downregulation of AR-FL upon AR antagonists' treatment led to a compensatory increase in AR-V7. Clinical samples showed significantly elevated expression of AR and AR-V7 in tumors compared to control cases. Further clinicopathological correlation revealed aggressive clinical traits, higher pathological grades, and poor survival with AR-V7 expression.
Conclusions: Our study unravels AR-V7 as a marker for poor clinical outcomes, predicting breast cancer aggressiveness, and encourages consideration of AR-V7 as a probable target for therapeutic intervention.
Competing Interests: Declarations Ethics approval and consent to participate This study was ethically approved from the Institute Ethics Committee for Postgraduate Research, All India Institute of Medical Sciences, New Delhi, vide Ref. No. IECPG-177/27.03.2019, RT-08/22.04.2019 dated April 29, 2019. Informed written consent from participants was obtained from the subjects prior to the recruitment into the study. The c. Consent for publication Not applicable. Competing interests The authors declare no competing interests.
(© 2024. The Author(s).)