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Role of SALL4 and Nodal in the prognosis and tamoxifen resistance of estrogen receptor-positive breast cancer

Despite the discovery of a number of different mechanisms underlying tamoxifen resistance, its molecular pathway is not completely clear. The upregulation of SALL4 and Nodal has been reported in breast cancer. Nevertheless, their role in tamoxifen resistance has not been investigated. In the present...

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Autores principales: Boustan, Arad, Mosaffa, Fatemeh, Jahangiri, Rosa, Heidarian-Miri, Hamid, Dahmardeh-Ghalehno, Asefeh, Jamialahmadi, Khadijeh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shiraz University 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340312/
https://www.ncbi.nlm.nih.gov/pubmed/34476264
http://dx.doi.org/10.22099/mbrc.2021.39878.1597
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author Boustan, Arad
Mosaffa, Fatemeh
Jahangiri, Rosa
Heidarian-Miri, Hamid
Dahmardeh-Ghalehno, Asefeh
Jamialahmadi, Khadijeh
author_facet Boustan, Arad
Mosaffa, Fatemeh
Jahangiri, Rosa
Heidarian-Miri, Hamid
Dahmardeh-Ghalehno, Asefeh
Jamialahmadi, Khadijeh
author_sort Boustan, Arad
collection PubMed
description Despite the discovery of a number of different mechanisms underlying tamoxifen resistance, its molecular pathway is not completely clear. The upregulation of SALL4 and Nodal has been reported in breast cancer. Nevertheless, their role in tamoxifen resistance has not been investigated. In the present study, we compared Nodal and SALL4 expression in 72 tamoxifen sensitive (TAMS) and tamoxifen-resistant (TAMR) patients. Afterward, the correlation of expression data with clinicopathological features and survival of patients was studied. Results showed that both SALL4 and Nodal were significantly upregulated in TAMR compared to TAMS patients. Besides, there was a positive association between Nodal and SALL4 expression. Furthermore, we evaluated their correlation with the expression of Oct4, Nanog and Sox2 stemness markers. The results demonstrated that in most tissue samples there was a positive correlation between Nodal and SALL4 expression with these stemness markers. Besides, the overexpression of SALL4 and Nodal significantly correlated with the N stage. Moreover, the overexpression of SALL4 was associated with extracapsular invasion and lymphatic invasion. High level expressions of SALL4 and Nodal had a significant association with worse disease-free survival (DFS) rates. In addition, increased level of Nodal expression provides a superior predictor factor for DFS. The multivariate Cox regression analysis also revealed that for DFS, perineural invasion (PNI) was independently an unfavorable prognostic value. These findings suggest that the high expression of SALL4 and Nodal could contribute to tamoxifen resistance and worse survival rates in tamoxifen-treated ER(+) breast cancer patients.
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spelling pubmed-83403122021-09-01 Role of SALL4 and Nodal in the prognosis and tamoxifen resistance of estrogen receptor-positive breast cancer Boustan, Arad Mosaffa, Fatemeh Jahangiri, Rosa Heidarian-Miri, Hamid Dahmardeh-Ghalehno, Asefeh Jamialahmadi, Khadijeh Mol Biol Res Commun Original Article Despite the discovery of a number of different mechanisms underlying tamoxifen resistance, its molecular pathway is not completely clear. The upregulation of SALL4 and Nodal has been reported in breast cancer. Nevertheless, their role in tamoxifen resistance has not been investigated. In the present study, we compared Nodal and SALL4 expression in 72 tamoxifen sensitive (TAMS) and tamoxifen-resistant (TAMR) patients. Afterward, the correlation of expression data with clinicopathological features and survival of patients was studied. Results showed that both SALL4 and Nodal were significantly upregulated in TAMR compared to TAMS patients. Besides, there was a positive association between Nodal and SALL4 expression. Furthermore, we evaluated their correlation with the expression of Oct4, Nanog and Sox2 stemness markers. The results demonstrated that in most tissue samples there was a positive correlation between Nodal and SALL4 expression with these stemness markers. Besides, the overexpression of SALL4 and Nodal significantly correlated with the N stage. Moreover, the overexpression of SALL4 was associated with extracapsular invasion and lymphatic invasion. High level expressions of SALL4 and Nodal had a significant association with worse disease-free survival (DFS) rates. In addition, increased level of Nodal expression provides a superior predictor factor for DFS. The multivariate Cox regression analysis also revealed that for DFS, perineural invasion (PNI) was independently an unfavorable prognostic value. These findings suggest that the high expression of SALL4 and Nodal could contribute to tamoxifen resistance and worse survival rates in tamoxifen-treated ER(+) breast cancer patients. Shiraz University 2021-09 /pmc/articles/PMC8340312/ /pubmed/34476264 http://dx.doi.org/10.22099/mbrc.2021.39878.1597 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Boustan, Arad
Mosaffa, Fatemeh
Jahangiri, Rosa
Heidarian-Miri, Hamid
Dahmardeh-Ghalehno, Asefeh
Jamialahmadi, Khadijeh
Role of SALL4 and Nodal in the prognosis and tamoxifen resistance of estrogen receptor-positive breast cancer
title Role of SALL4 and Nodal in the prognosis and tamoxifen resistance of estrogen receptor-positive breast cancer
title_full Role of SALL4 and Nodal in the prognosis and tamoxifen resistance of estrogen receptor-positive breast cancer
title_fullStr Role of SALL4 and Nodal in the prognosis and tamoxifen resistance of estrogen receptor-positive breast cancer
title_full_unstemmed Role of SALL4 and Nodal in the prognosis and tamoxifen resistance of estrogen receptor-positive breast cancer
title_short Role of SALL4 and Nodal in the prognosis and tamoxifen resistance of estrogen receptor-positive breast cancer
title_sort role of sall4 and nodal in the prognosis and tamoxifen resistance of estrogen receptor-positive breast cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340312/
https://www.ncbi.nlm.nih.gov/pubmed/34476264
http://dx.doi.org/10.22099/mbrc.2021.39878.1597
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