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Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer
PURPOSE: Nucleolar protein 10 (NOP10) is required for ribosome biogenesis and telomere maintenance and plays a key role in carcinogenesis. This study aims to evaluate the clinical and prognostic significance of NOP10 in breast cancer (BC). METHODS: NOP10 expression was assessed at mRNA level employi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920889/ https://www.ncbi.nlm.nih.gov/pubmed/33161513 http://dx.doi.org/10.1007/s10549-020-05999-3 |
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author | Elsharawy, Khloud A. Althobiti, Maryam Mohammed, Omar J. Aljohani, Abrar I. Toss, Michael S. Green, Andrew R. Rakha, Emad A. |
author_facet | Elsharawy, Khloud A. Althobiti, Maryam Mohammed, Omar J. Aljohani, Abrar I. Toss, Michael S. Green, Andrew R. Rakha, Emad A. |
author_sort | Elsharawy, Khloud A. |
collection | PubMed |
description | PURPOSE: Nucleolar protein 10 (NOP10) is required for ribosome biogenesis and telomere maintenance and plays a key role in carcinogenesis. This study aims to evaluate the clinical and prognostic significance of NOP10 in breast cancer (BC). METHODS: NOP10 expression was assessed at mRNA level employing the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1980) and Cancer Genome Atlas (TCGA) BC cohorts (n = 854). Protein expression was evaluated on tissue microarray of a large BC cohort (n = 1081) using immunohistochemistry. The correlation between NOP10 expression, clinicopathological parameters and patient outcome was assessed. RESULTS: NOP10 expression was detected in the nucleus and nucleolus of the tumour cells. At the transcriptomic and proteomic levels, NOP10 was significantly associated with aggressive BC features including high tumour grade, high nucleolar score and poor Nottingham Prognostic Index. High NOP10 protein expression was an independent predictor of poor outcome in the whole cohort and in triple-negative BC (TNBC) class (p = 0.002 & p = 0.014, respectively). In chemotherapy- treated patients, high NOP10 protein expression was significantly associated with shorter survival (p = 0.03) and was predictive of higher risk of death (p = 0.028) and development of distant metastasis (p = 0.02) independent of tumour size, nodal stage and tumour grade. CONCLUSION: High NOP10 expression is a poor prognostic biomarker in BC and its expression can help in predicting chemotherapy resistance. Functional assessments are necessary to decipher the underlying mechanisms and to reveal its potential therapeutic values in various BC subtypes especially in the aggressive TNBC class. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-020-05999-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7920889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-79208892021-03-18 Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer Elsharawy, Khloud A. Althobiti, Maryam Mohammed, Omar J. Aljohani, Abrar I. Toss, Michael S. Green, Andrew R. Rakha, Emad A. Breast Cancer Res Treat Preclinical Study PURPOSE: Nucleolar protein 10 (NOP10) is required for ribosome biogenesis and telomere maintenance and plays a key role in carcinogenesis. This study aims to evaluate the clinical and prognostic significance of NOP10 in breast cancer (BC). METHODS: NOP10 expression was assessed at mRNA level employing the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1980) and Cancer Genome Atlas (TCGA) BC cohorts (n = 854). Protein expression was evaluated on tissue microarray of a large BC cohort (n = 1081) using immunohistochemistry. The correlation between NOP10 expression, clinicopathological parameters and patient outcome was assessed. RESULTS: NOP10 expression was detected in the nucleus and nucleolus of the tumour cells. At the transcriptomic and proteomic levels, NOP10 was significantly associated with aggressive BC features including high tumour grade, high nucleolar score and poor Nottingham Prognostic Index. High NOP10 protein expression was an independent predictor of poor outcome in the whole cohort and in triple-negative BC (TNBC) class (p = 0.002 & p = 0.014, respectively). In chemotherapy- treated patients, high NOP10 protein expression was significantly associated with shorter survival (p = 0.03) and was predictive of higher risk of death (p = 0.028) and development of distant metastasis (p = 0.02) independent of tumour size, nodal stage and tumour grade. CONCLUSION: High NOP10 expression is a poor prognostic biomarker in BC and its expression can help in predicting chemotherapy resistance. Functional assessments are necessary to decipher the underlying mechanisms and to reveal its potential therapeutic values in various BC subtypes especially in the aggressive TNBC class. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-020-05999-3) contains supplementary material, which is available to authorized users. Springer US 2020-11-08 2021 /pmc/articles/PMC7920889/ /pubmed/33161513 http://dx.doi.org/10.1007/s10549-020-05999-3 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 Elsharawy, Khloud A. Althobiti, Maryam Mohammed, Omar J. Aljohani, Abrar I. Toss, Michael S. Green, Andrew R. Rakha, Emad A. Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer |
title | Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer |
title_full | Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer |
title_fullStr | Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer |
title_full_unstemmed | Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer |
title_short | Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer |
title_sort | nucleolar protein 10 (nop10) predicts poor prognosis in invasive breast cancer |
topic | Preclinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920889/ https://www.ncbi.nlm.nih.gov/pubmed/33161513 http://dx.doi.org/10.1007/s10549-020-05999-3 |
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