Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer

Abstract We here examined whether Nestin, by protein and mRNA levels, could be a predictor of BRCA1 related breast cancer, a basal-like phenotype, and aggressive tumours. Immunohistochemical staining of Nestin was done in independent breast cancer hospital cohorts (Series I-V, total 1257 cases). Als...

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Autores principales:	Kristi Krüger, Elisabeth Wik, Gøril Knutsvik, Hawa Nalwoga, Tor A. Klingen, Jarle B. Arnes, Ying Chen, Monica Mannelqvist, Konstantina Dimitrakopoulou, Ingunn M. Stefansson, Even Birkeland, Turid Aas, Nicholas P. Tobin, Inge Jonassen, Jonas Bergh, William D. Foulkes, Lars A. Akslen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2a8a20fe1d2e4fe7af3fd1ff76db984e
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spelling	oai:doaj.org-article:2a8a20fe1d2e4fe7af3fd1ff76db984e2021-12-02T11:53:11ZExpression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer10.1038/s41598-017-00862-w2045-2322https://doaj.org/article/2a8a20fe1d2e4fe7af3fd1ff76db984e2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00862-whttps://doaj.org/toc/2045-2322Abstract We here examined whether Nestin, by protein and mRNA levels, could be a predictor of BRCA1 related breast cancer, a basal-like phenotype, and aggressive tumours. Immunohistochemical staining of Nestin was done in independent breast cancer hospital cohorts (Series I-V, total 1257 cases). Also, TCGA proteomic data (n = 103), mRNA microarray data from TCGA (n = 520), METABRIC (n = 1992), and 6 open access breast cancer datasets (n = 1908) were analysed. Patients with Nestin protein expression in tumour cells more often had BRCA1 germline mutations (OR 8.7, p < 0.0005, Series III), especially among younger patients (<40 years at diagnosis) (OR 16.5, p = 0.003). Nestin protein positivity, observed in 9–28% of our hospital cases (Series I-IV), was independently associated with reduced breast cancer specific survival (HR = 2.0, p = 0.035) and was consistently related to basal-like differentiation (by Cytokeratin 5, OR 8.7–13.8, p < 0.0005; P-cadherin OR 7.0–8.9, p < 0.0005; EGFR staining, OR 3.7–8.2, p ≤ 0.05). Nestin mRNA correlated significantly with Nestin protein expression (ρ = 0.6, p < 0.0005), and high levels were seen in the basal-like intrinsic subtype. Gene expression signalling pathways linked to high Nestin were explored, and revealed associations with stem-like tumour features. In summary, Nestin was strongly associated with germline BRCA1 related breast cancer, a basal-like phenotype, reduced survival, and stemness characteristics.Kristi KrügerElisabeth WikGøril KnutsvikHawa NalwogaTor A. KlingenJarle B. ArnesYing ChenMonica MannelqvistKonstantina DimitrakopoulouIngunn M. StefanssonEven BirkelandTurid AasNicholas P. TobinInge JonassenJonas BerghWilliam D. FoulkesLars A. AkslenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kristi Krüger Elisabeth Wik Gøril Knutsvik Hawa Nalwoga Tor A. Klingen Jarle B. Arnes Ying Chen Monica Mannelqvist Konstantina Dimitrakopoulou Ingunn M. Stefansson Even Birkeland Turid Aas Nicholas P. Tobin Inge Jonassen Jonas Bergh William D. Foulkes Lars A. Akslen Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer
description	Abstract We here examined whether Nestin, by protein and mRNA levels, could be a predictor of BRCA1 related breast cancer, a basal-like phenotype, and aggressive tumours. Immunohistochemical staining of Nestin was done in independent breast cancer hospital cohorts (Series I-V, total 1257 cases). Also, TCGA proteomic data (n = 103), mRNA microarray data from TCGA (n = 520), METABRIC (n = 1992), and 6 open access breast cancer datasets (n = 1908) were analysed. Patients with Nestin protein expression in tumour cells more often had BRCA1 germline mutations (OR 8.7, p < 0.0005, Series III), especially among younger patients (<40 years at diagnosis) (OR 16.5, p = 0.003). Nestin protein positivity, observed in 9–28% of our hospital cases (Series I-IV), was independently associated with reduced breast cancer specific survival (HR = 2.0, p = 0.035) and was consistently related to basal-like differentiation (by Cytokeratin 5, OR 8.7–13.8, p < 0.0005; P-cadherin OR 7.0–8.9, p < 0.0005; EGFR staining, OR 3.7–8.2, p ≤ 0.05). Nestin mRNA correlated significantly with Nestin protein expression (ρ = 0.6, p < 0.0005), and high levels were seen in the basal-like intrinsic subtype. Gene expression signalling pathways linked to high Nestin were explored, and revealed associations with stem-like tumour features. In summary, Nestin was strongly associated with germline BRCA1 related breast cancer, a basal-like phenotype, reduced survival, and stemness characteristics.
format	article
author	Kristi Krüger Elisabeth Wik Gøril Knutsvik Hawa Nalwoga Tor A. Klingen Jarle B. Arnes Ying Chen Monica Mannelqvist Konstantina Dimitrakopoulou Ingunn M. Stefansson Even Birkeland Turid Aas Nicholas P. Tobin Inge Jonassen Jonas Bergh William D. Foulkes Lars A. Akslen
author_facet	Kristi Krüger Elisabeth Wik Gøril Knutsvik Hawa Nalwoga Tor A. Klingen Jarle B. Arnes Ying Chen Monica Mannelqvist Konstantina Dimitrakopoulou Ingunn M. Stefansson Even Birkeland Turid Aas Nicholas P. Tobin Inge Jonassen Jonas Bergh William D. Foulkes Lars A. Akslen
author_sort	Kristi Krüger
title	Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer
title_short	Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer
title_full	Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer
title_fullStr	Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer
title_full_unstemmed	Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer
title_sort	expression of nestin associates with brca1 mutations, a basal-like phenotype and aggressive breast cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2a8a20fe1d2e4fe7af3fd1ff76db984e
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Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer

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