TY - JOUR
T1 - Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes
AU - Nguyen Van Long, Flora
AU - Lardy-Cleaud, Audrey
AU - Bray, Susan
AU - Chabaud, Sylvie
AU - Dubois, Thierry
AU - Diot, Alexandra
AU - Thompson, Alastair M.
AU - Bourdon, Jean-Christophe
AU - Perol, David
AU - Bouvet, Philippe
AU - Diaz, Jean-Jacques
AU - Marcel, Virginie
N1 - Funding: This research was funded by PAIR Sein program (ARC_INCa_LNCC_7625), Fondation ARC (20161204686 and 20171206356) and Ligue Contre le Cancer Comités Allier and Saône-et-Loire (PPE 2016). F.NVL was a recipient of a fellowship from Ligue Nationale Contre le Cancer (LNCC) and the Fondation pour la Recherche Médicale (FRM). A.D. and J.-C.B. are supported by Breast Cancer Now fellowship (2012MaySF127). The Tayside Tissue Bank is supported by the Chief Scientist Office (CSO), NHS, and Dundee University. Acknowledgments: We thank BioCOS Life Sciences for bioinformatics. We gratefully acknowledge the contribution to this publication made by the Tayside Tissue Bank (TTB, Dundee, Scotland, UK).
PY - 2018/10/22
Y1 - 2018/10/22
N2 - 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.
AB - 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.
KW - nucleolin
KW - breast cancer
KW - prognostic marker
KW - triple-negative breast cancer
U2 - 10.3390/cancers10100390
DO - 10.3390/cancers10100390
M3 - Article
C2 - 30360377
SN - 2072-6694
VL - 10
SP - 1
EP - 11
JO - Cancers
JF - Cancers
IS - 10
M1 - 390
ER -
