Racial Differences in Androgen Receptor (AR) and AR Splice Variants (AR-SVs) Expression in Treatment-Naïve Androgen-Dependent Prostate Cancer
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 Amer...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/3/648 |
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| author | Farhan Khan Obianuju Mercy Anelo Qandeel Sadiq Wendy Effah Gary Price Daniel L. Johnson Suriyan Ponnusamy Brandy Grimes Michelle L. Morrison Jay H. Fowke D. Neil Hayes Ramesh Narayanan |
| author_facet | Farhan Khan Obianuju Mercy Anelo Qandeel Sadiq Wendy Effah Gary Price Daniel L. Johnson Suriyan Ponnusamy Brandy Grimes Michelle L. Morrison Jay H. Fowke D. Neil Hayes Ramesh Narayanan |
| author_sort | Farhan Khan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T06:54:32Z |
| format | Article |
| id | doaj.art-6bcc6af54d354d46beb55bb163520772 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:54:32Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-6bcc6af54d354d46beb55bb1635207722023-11-17T09:43:33ZengMDPI AGBiomedicines2227-90592023-02-0111364810.3390/biomedicines11030648Racial Differences in Androgen Receptor (AR) and AR Splice Variants (AR-SVs) Expression in Treatment-Naïve Androgen-Dependent Prostate CancerFarhan Khan0Obianuju Mercy Anelo1Qandeel Sadiq2Wendy Effah3Gary Price4Daniel L. Johnson5Suriyan Ponnusamy6Brandy Grimes7Michelle L. Morrison8Jay H. Fowke9D. Neil Hayes10Ramesh Narayanan11Department of Pathology, Methodist Hospital, Memphis, TN 38104, USADepartment of Pathology, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Pathology, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Medicine, Division of Hematology and Oncology, University of Tennessee Health Science Center, Cancer Research Building 19, S. Manassas, Room 120 Memphis, Memphis, TN 38103, USADepartment of Medicine, Division of Hematology and Oncology, University of Tennessee Health Science Center, Cancer Research Building 19, S. Manassas, Room 120 Memphis, Memphis, TN 38103, USAMolecular Bioinformatics Core, University of Tennessee Health Science Center, Memphis, TN 38103, USADepartment of Medicine, Division of Hematology and Oncology, University of Tennessee Health Science Center, Cancer Research Building 19, S. Manassas, Room 120 Memphis, Memphis, TN 38103, USAWest Cancer Center, Memphis, TN 38138, USABiorepository Core, UTHSC Center for Cancer Research, Memphis, TN 38103, USADepartment of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Medicine, Division of Hematology and Oncology, University of Tennessee Health Science Center, Cancer Research Building 19, S. Manassas, Room 120 Memphis, Memphis, TN 38103, USADepartment of Medicine, Division of Hematology and Oncology, University of Tennessee Health Science Center, Cancer Research Building 19, S. Manassas, Room 120 Memphis, Memphis, TN 38103, USAAndrogen 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.https://www.mdpi.com/2227-9059/11/3/648androgen receptor (AR)AR splice variants (AR-SV)prostate cancercastration-resistant prostate cancer (CRPC)raceAfrican American (AA) |
| spellingShingle | Farhan Khan Obianuju Mercy Anelo Qandeel Sadiq Wendy Effah Gary Price Daniel L. Johnson Suriyan Ponnusamy Brandy Grimes Michelle L. Morrison Jay H. Fowke D. Neil Hayes Ramesh Narayanan Racial Differences in Androgen Receptor (AR) and AR Splice Variants (AR-SVs) Expression in Treatment-Naïve Androgen-Dependent Prostate Cancer Biomedicines androgen receptor (AR) AR splice variants (AR-SV) prostate cancer castration-resistant prostate cancer (CRPC) race African American (AA) |
| title | Racial Differences in Androgen Receptor (AR) and AR Splice Variants (AR-SVs) Expression in Treatment-Naïve Androgen-Dependent Prostate Cancer |
| title_full | Racial Differences in Androgen Receptor (AR) and AR Splice Variants (AR-SVs) Expression in Treatment-Naïve Androgen-Dependent Prostate Cancer |
| title_fullStr | Racial Differences in Androgen Receptor (AR) and AR Splice Variants (AR-SVs) Expression in Treatment-Naïve Androgen-Dependent Prostate Cancer |
| title_full_unstemmed | Racial Differences in Androgen Receptor (AR) and AR Splice Variants (AR-SVs) Expression in Treatment-Naïve Androgen-Dependent Prostate Cancer |
| title_short | Racial Differences in Androgen Receptor (AR) and AR Splice Variants (AR-SVs) Expression in Treatment-Naïve Androgen-Dependent Prostate Cancer |
| title_sort | racial differences in androgen receptor ar and ar splice variants ar svs expression in treatment naive androgen dependent prostate cancer |
| topic | androgen receptor (AR) AR splice variants (AR-SV) prostate cancer castration-resistant prostate cancer (CRPC) race African American (AA) |
| url | https://www.mdpi.com/2227-9059/11/3/648 |
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