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Cancers 2018, 10(10), 390; https://doi.org/10.3390/cancers10100390

Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes

1
Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, CEDEX 08, 69373 Lyon, France
2
Department of Clinical Research, Léon Bérard Cancer Centre, 28 rue Laennec, 69008 Lyon, France
3
Tayside Tissue Bank, Ninewells Hospital and Medical School, NHS Tayside, Dundee DD1 9SY, Scotland, UK
4
Breast Cancer Biology Group, Translational Research Department, PSL Research University, Institut Curie, 26 rue d’Ulm, 75005 Paris, France
5
Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
6
Department of Pathology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
7
Olga Keith Wiess Chair of Surgery, Dan L. Duncan Breast Center, Division of Surgical Oncology, Baylor College of Medicine, Houston, TX 77030, USA
8
Ecole Normale Supérieure de Lyon, Université de Lyon, CEDEX 07, 69342 Lyon, France
*
Authors to whom correspondence should be addressed.
Co-senior authors.
Received: 31 July 2018 / Revised: 12 October 2018 / Accepted: 18 October 2018 / Published: 22 October 2018
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Abstract

Background: Nucleolin (NCL) is a multifunctional protein with oncogenic properties. Anti-NCL drugs show strong cytotoxic effects, including in triple-negative breast cancer (TNBC) models, and are currently being evaluated in phase II clinical trials. However, few studies have investigated the clinical value of NCL and whether NCL stratified cancer patients. Here, we have investigated for the first time the association of NCL with clinical characteristics in breast cancers independently of the different subtypes. Methods: Using two independent series (n = 216; n = 661), we evaluated the prognostic value of NCL in non-metastatic breast cancers using univariate and/or multivariate Cox-regression analyses. Results: We reported that NCL mRNA expression levels are markers of poor survivals independently of tumour size and lymph node invasion status (n = 216). In addition, an association of NCL expression levels with poor survival was observed in TNBC (n = 40, overall survival (OS) p = 0.0287, disease-free survival (DFS) p = 0.0194). Transcriptomic analyses issued from The Cancer Genome Atlas (TCGA) database (n = 661) revealed that breast tumours expressing either low or high NCL mRNA expression levels exhibit different gene expression profiles. These data suggest that tumours expressing high NCL mRNA levels are different from those expressing low NCL mRNA levels. Conclusions: NCL is an independent marker of prognosis in breast cancers. We anticipated that anti-NCL is a promising therapeutic strategy that could rapidly be evaluated in high NCL-expressing tumours to improve breast cancer management. View Full-Text
Keywords: nucleolin; breast cancer; prognostic marker; triple-negative breast cancer nucleolin; breast cancer; prognostic marker; triple-negative breast cancer
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Nguyen Van Long, F.; Lardy-Cleaud, A.; Bray, S.; Chabaud, S.; Dubois, T.; Diot, A.; Jordan, L.B.; Thompson, A.M.; Bourdon, J.-C.; Perol, D.; Bouvet, P.; Diaz, J.-J.; Marcel, V. Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes. Cancers 2018, 10, 390.

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