Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer
Kruger, Kristi; Wik, Elisabeth; Knutsvik, Gøril; Nalwoga, Hawa; Klingen, Tor Audun; Arnes, Jarle; Chen, Ying; Mannelqvist, Monica; Dimitrakopoulou, Konstantina; Stefansson, Ingunn; Birkeland, Even; Aas, Turid; Tobin, Nicholas P; Jonassen, Inge; Bergh, Jonas; Foulkes, William D; Akslen, Lars A
Journal article, Peer reviewed
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https://hdl.handle.net/10642/7287Utgivelsesdato
2017-04-24Metadata
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Krüger, K., Wik, E., Knutsvik, G., Nalwoga, H., Klingen, T. A., Arnes, J. B., ... & Birkeland, E. (2017). Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer. Scientific reports, 7(1), 1089. https://doi.org/10.1038/s41598-017-00862-wSammendrag
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.