Development and Validation of a New BAG-1L-Specific Antibody to Quantify BAG-1L Protein Expression in Advanced Prostate Cancer.
Date
2023-08-29ICR Author
Author
Neeb, A
Figueiredo, I
Gurel, B
Nava Rodrigues, D
Rekowski, J
Riisnaes, R
Ferreira, A
Miranda, S
Crespo, M
Westaby, D
de Los Dolores Fenor de La Maza, M
Guo, C
Carmichael, J
Grochot, R
Tunariu, N
Cato, ACB
Plymate, SR
de Bono, JS
Sharp, A
Type
Journal Article
Metadata
Show full item recordAbstract
BCL-2-associated athanogene-1L (BAG-1L) is a critical co-regulator that binds to and enhances the transactivation function of the androgen receptor, leading to prostate cancer development and progression. Studies investigating the clinical importance of BAG-1L protein expression in advanced prostate cancer have been limited by the paucity of antibodies that specifically recognize the long isoform. In this study, we developed and validated a new BAG-1L-specific antibody using multiple orthogonal methods across several cell lines with and without genomic manipulation of BAG-1L and all BAG-1 isoforms. Following this, we performed exploratory immunohistochemistry to determine BAG-1L protein expression in normal human, matched castration-sensitive prostate cancer (CSPC) and castration-resistant prostate cancer (CRPC), unmatched primary and metastatic CRPC, and early breast cancer tissues. We demonstrated higher BAG-1L protein expression in CRPC metastases than in unmatched, untreated, castration-sensitive prostatectomies from men who remained recurrence-free for 5 years. In contrast, BAG-1L protein expression did not change between matched, same patient, CSPC and CRPC biopsies, suggesting that BAG-1L protein expression may be associated with more aggressive biology and the development of castration resistance. Finally, in a cohort of patients who universally developed CRPC, there was no association between BAG-1L protein expression at diagnosis and time to CRPC or overall survival, and no association between BAG-1L protein expression at CRPC biopsy and clinical outcome from androgen receptor targeting therapies or docetaxel chemotherapy. The limitations of this study include the requirement to validate the reproducibility of the assay developed, the potential influence of pre-analytical factors, timing of CRPC biopsies, relatively small patient numbers, and heterogenous therapies on BAG-1L protein expression, and the clinical outcome analyses performed. We describe a new BAG-1L-specific antibody that the research community can further develop to elucidate the biological and clinical significance of BAG-1L protein expression in malignant and nonmalignant diseases.
Collections
Subject
BAG-1L
advanced prostate cancer
androgen receptor
biomarker
immunohistochemistry
treatment resistance
Research team
Cancer Biomarkers
Translational Therapeutic
PrCa Targeted Therapy
Language
eng
Date accepted
2023-08-18
License start date
2023-08-29
Citation
Laboratory Investigation, 2023, 103 (11), pp. 100245 -
Publisher
ELSEVIER SCIENCE INC