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Racial Differences in Androgen Receptor (AR) and AR Splice Variants (AR-SVs) Expression in Treatment-Naïve Androgen-Dependent Prostate Cancer. | LitMetric

AI Article Synopsis

  • Androgen receptor splice variants (AR-SVs), like AR-V7, are linked to the aggressive growth of castration-resistant prostate cancer (CRPC), affecting about 30% of cases but are less common in initial prostate cancer diagnoses.
  • African American men tend to get diagnosed with more aggressive prostate cancer and have shorter survival rates compared to Caucasian American men, which led researchers to explore AR-SVs as potential indicators of aggressive cancer growth.
  • Tissue analysis showed that while AR-V7 was found in some African American tumors, other AR-SVs might also be present, suggesting that these variants occur more frequently in primary prostate cancer than previously thought, prompting further studies on their role in treatment strategies.

Article Abstract

Androgen receptor splice variants (AR-SVs) contribute to the aggressive growth of castration-resistant prostate cancer (CRPC). AR-SVs, including AR-V7, are expressed in ~30% of CRPC, but minimally in treatment-naïve primary prostate cancer (PCa). Compared to Caucasian American (CA) men, African American (AA) men are more likely to be diagnosed with aggressive/potentially lethal PCa and have shorter disease-free survival. Expression of a truncated AR in an aggressively growing patient-derived xenograft developed with a primary PCa specimen from an AA patient led us to hypothesize that the expression of AR-SVs could be an indicator of aggressive growth both in PCa progression and at the CRPC stage in AA men. Tissue microarrays (TMAs) were created from formalin-fixed paraffin-embedded (FFPE) prostatectomy tumor blocks from 118 AA and 115 CA treatment-naïve PCa patients. TMAs were stained with AR-V7-speicifc antibody and with antibodies binding to the N-terminus domain (NTD) and ligand-binding domain (LBD) of the AR. Since over 20 AR-SVs have been identified, and most AR-SVs do not as yet have a specific antibody, we considered a 2.0-fold or greater difference in the NTD vs. LBD staining as indication of potential AR-SV expression. Two AA, but no CA, patient tumors stained positively for AR-V7. AR staining with NTD and LBD antibodies was robust in most patients, with 21% of patients staining at least 2-fold more for NTD than LBD, indicating that AR-SVs other than AR-V7 are expressed in primary treatment-naïve PCa. About 24% of the patients were AR-negative, and race differences in AR expression were not statistically significant. These results indicate that AR-SVs are not restricted to CRPC, but also are expressed in primary PCa at higher rate than previously reported. Future investigation of the relative expression of NTD vs. LBD AR-SVs could guide the use of newly developed treatments targeting the NTD earlier in the treatment paradigm.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044992PMC
http://dx.doi.org/10.3390/biomedicines11030648DOI Listing

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