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Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer

BACKGROUND: Breast cancer (BC) is a disease with variable morphology, clinical behaviour and response to therapy. Identifying factors associated with the progression of early-stage BC can help understand the risk of metastasis and guide treatment decisions. Myxovirus resistance 1 (MX1), which is inv...

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Autores principales: Aljohani, Abrar I., Joseph, Chitra, Kurozumi, Sasagu, Mohammed, Omar J., Miligy, Islam M., Green, Andrew R., Rakha, Emad A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220876/
https://www.ncbi.nlm.nih.gov/pubmed/32350677
http://dx.doi.org/10.1007/s10549-020-05646-x
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author Aljohani, Abrar I.
Joseph, Chitra
Kurozumi, Sasagu
Mohammed, Omar J.
Miligy, Islam M.
Green, Andrew R.
Rakha, Emad A.
author_facet Aljohani, Abrar I.
Joseph, Chitra
Kurozumi, Sasagu
Mohammed, Omar J.
Miligy, Islam M.
Green, Andrew R.
Rakha, Emad A.
author_sort Aljohani, Abrar I.
collection PubMed
description BACKGROUND: Breast cancer (BC) is a disease with variable morphology, clinical behaviour and response to therapy. Identifying factors associated with the progression of early-stage BC can help understand the risk of metastasis and guide treatment decisions. Myxovirus resistance 1 (MX1), which is involved in the cellular antiviral mechanism, plays a role in some solid tumours; however, its role in invasive BC remains unknown. In this study, we aimed to explore the clinicopathological and prognostic significance of MX1 in BC. METHODS: MX1 was assessed at the protein level using tissue microarrays from a large well-annotated BC cohort (n = 845). The expression of MX1 mRNA was assessed at the transcriptomic level using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n = 1980) and validated using three publicly available cohorts on Breast Cancer Gene-Expression Miner (bc-GenExMiner version 4.4). The associations between MX1 expression and clinicopathological factors, and outcome were evaluated. RESULTS: High MX1 protein expression was associated with features of aggressiveness, including large tumour size, high tumour grade, high Nottingham prognostic index scores, hormone receptor negativity and high Ki67 expression. High MX1 expression showed an association with poor patient outcome and it was an independent predictor of short BC-specific survival (p = 0.028; HR = 1.5; 95% CI = 1.0–2.2). Consistent with the protein results, high MX1 mRNA levels showed an association with features of aggressive behaviour and with shorter survival. CONCLUSION: This study identified MX1 as an independent predictor of poor outcome in patients with BC. Further functional studies are needed to investigate the biological role of MX1 in BC and its potential value as a therapeutic target. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-020-05646-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-72208762020-05-14 Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer Aljohani, Abrar I. Joseph, Chitra Kurozumi, Sasagu Mohammed, Omar J. Miligy, Islam M. Green, Andrew R. Rakha, Emad A. Breast Cancer Res Treat Preclinical Study BACKGROUND: Breast cancer (BC) is a disease with variable morphology, clinical behaviour and response to therapy. Identifying factors associated with the progression of early-stage BC can help understand the risk of metastasis and guide treatment decisions. Myxovirus resistance 1 (MX1), which is involved in the cellular antiviral mechanism, plays a role in some solid tumours; however, its role in invasive BC remains unknown. In this study, we aimed to explore the clinicopathological and prognostic significance of MX1 in BC. METHODS: MX1 was assessed at the protein level using tissue microarrays from a large well-annotated BC cohort (n = 845). The expression of MX1 mRNA was assessed at the transcriptomic level using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n = 1980) and validated using three publicly available cohorts on Breast Cancer Gene-Expression Miner (bc-GenExMiner version 4.4). The associations between MX1 expression and clinicopathological factors, and outcome were evaluated. RESULTS: High MX1 protein expression was associated with features of aggressiveness, including large tumour size, high tumour grade, high Nottingham prognostic index scores, hormone receptor negativity and high Ki67 expression. High MX1 expression showed an association with poor patient outcome and it was an independent predictor of short BC-specific survival (p = 0.028; HR = 1.5; 95% CI = 1.0–2.2). Consistent with the protein results, high MX1 mRNA levels showed an association with features of aggressive behaviour and with shorter survival. CONCLUSION: This study identified MX1 as an independent predictor of poor outcome in patients with BC. Further functional studies are needed to investigate the biological role of MX1 in BC and its potential value as a therapeutic target. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-020-05646-x) contains supplementary material, which is available to authorized users. Springer US 2020-04-29 2020 /pmc/articles/PMC7220876/ /pubmed/32350677 http://dx.doi.org/10.1007/s10549-020-05646-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Preclinical Study
Aljohani, Abrar I.
Joseph, Chitra
Kurozumi, Sasagu
Mohammed, Omar J.
Miligy, Islam M.
Green, Andrew R.
Rakha, Emad A.
Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer
title Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer
title_full Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer
title_fullStr Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer
title_full_unstemmed Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer
title_short Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer
title_sort myxovirus resistance 1 (mx1) is an independent predictor of poor outcome in invasive breast cancer
topic Preclinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220876/
https://www.ncbi.nlm.nih.gov/pubmed/32350677
http://dx.doi.org/10.1007/s10549-020-05646-x
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