AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors
The co-expression of androgen (AR) and estrogen (ER) receptors, in terms of higher AR/ER ratio, has been recently associated with poor outcome in ER-positive (ER+) breast cancer (BC) patients. The aim of this study was to analyze if the biological aggressiveness, underlined in ER+ BC tumors with hig...
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2020-04-01
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author | Nelson Rangel Milena Rondon-Lagos Laura Annaratone Andrés Felipe Aristizábal-Pachon Paola Cassoni Anna Sapino Isabella Castellano |
author_facet | Nelson Rangel Milena Rondon-Lagos Laura Annaratone Andrés Felipe Aristizábal-Pachon Paola Cassoni Anna Sapino Isabella Castellano |
author_sort | Nelson Rangel |
collection | DOAJ |
description | The co-expression of androgen (AR) and estrogen (ER) receptors, in terms of higher AR/ER ratio, has been recently associated with poor outcome in ER-positive (ER+) breast cancer (BC) patients. The aim of this study was to analyze if the biological aggressiveness, underlined in ER+ BC tumors with higher AR/ER ratio, could be due to higher expression of genes related to cell proliferation. On a cohort of 47 ER+ BC patients, the AR/ER ratio was assessed by immunohistochemistry and by mRNA analysis. The expression level of five gene proliferation markers was defined through TaqMan<sup>®</sup>-qPCR assays. Results were validated using 979 BC cases obtained from gene expression public databases. ER+ BC tumors with ratios of AR/ER ≥ 2 have higher expression levels of cellular proliferation genes than tumors with ratios of AR/ER < 2, in both the 47 ER+ BC patients (<i>P</i> < 0.001) and in the validation cohort (<i>P</i> = 0.005). Moreover, BC cases with ratios of AR/ER ≥ 2 of the validation cohort were mainly assigned to luminal B and HER2-enriched molecular subtypes, typically characterized by higher proliferation and poorer prognosis. These data suggest that joint routine evaluation of AR and ER expression may identify a unique subset of tumors, which show higher levels of cellular proliferation and therefore a more aggressive behavior. |
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id | doaj.art-f3c69f51b3184e74b4dadfac62af351b |
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issn | 2073-4409 |
language | English |
last_indexed | 2024-03-10T20:15:59Z |
publishDate | 2020-04-01 |
publisher | MDPI AG |
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series | Cells |
spelling | doaj.art-f3c69f51b3184e74b4dadfac62af351b2023-11-19T22:37:48ZengMDPI AGCells2073-44092020-04-0194106410.3390/cells9041064AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast TumorsNelson Rangel0Milena Rondon-Lagos1Laura Annaratone2Andrés Felipe Aristizábal-Pachon3Paola Cassoni4Anna Sapino5Isabella Castellano6School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, Tunja 150003, ColombiaSchool of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, Tunja 150003, ColombiaDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá 110231, ColombiaDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, University of Turin, 10126 Turin, ItalyThe co-expression of androgen (AR) and estrogen (ER) receptors, in terms of higher AR/ER ratio, has been recently associated with poor outcome in ER-positive (ER+) breast cancer (BC) patients. The aim of this study was to analyze if the biological aggressiveness, underlined in ER+ BC tumors with higher AR/ER ratio, could be due to higher expression of genes related to cell proliferation. On a cohort of 47 ER+ BC patients, the AR/ER ratio was assessed by immunohistochemistry and by mRNA analysis. The expression level of five gene proliferation markers was defined through TaqMan<sup>®</sup>-qPCR assays. Results were validated using 979 BC cases obtained from gene expression public databases. ER+ BC tumors with ratios of AR/ER ≥ 2 have higher expression levels of cellular proliferation genes than tumors with ratios of AR/ER < 2, in both the 47 ER+ BC patients (<i>P</i> < 0.001) and in the validation cohort (<i>P</i> = 0.005). Moreover, BC cases with ratios of AR/ER ≥ 2 of the validation cohort were mainly assigned to luminal B and HER2-enriched molecular subtypes, typically characterized by higher proliferation and poorer prognosis. These data suggest that joint routine evaluation of AR and ER expression may identify a unique subset of tumors, which show higher levels of cellular proliferation and therefore a more aggressive behavior.https://www.mdpi.com/2073-4409/9/4/1064breast cancerandrogen receptorestrogen receptorcrosstalk of nuclear receptorsproliferation genes |
spellingShingle | Nelson Rangel Milena Rondon-Lagos Laura Annaratone Andrés Felipe Aristizábal-Pachon Paola Cassoni Anna Sapino Isabella Castellano AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors Cells breast cancer androgen receptor estrogen receptor crosstalk of nuclear receptors proliferation genes |
title | AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors |
title_full | AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors |
title_fullStr | AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors |
title_full_unstemmed | AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors |
title_short | AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors |
title_sort | ar er ratio correlates with expression of proliferation markers and with distinct subset of breast tumors |
topic | breast cancer androgen receptor estrogen receptor crosstalk of nuclear receptors proliferation genes |
url | https://www.mdpi.com/2073-4409/9/4/1064 |
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