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

Flora Nguyen Van Long, Audrey Lardy-Cleaud, Susan Bray, Sylvie Chabaud, Thierry Dubois, Alexandra Diot, Alastair M. Thompson, Jean-Christophe Bourdon, David Perol, Philippe Bouvet, Jean-Jacques Diaz (Lead / Corresponding author), Virginie Marcel (Lead / Corresponding author)

Research output: Contribution to journalArticle

68 Downloads (Pure)

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.

Original languageEnglish
Article number390
Pages (from-to)1-11
Number of pages11
JournalCancers
Volume10
Issue number10
DOIs
Publication statusPublished - 22 Oct 2018

Fingerprint

Biological Phenomena
Breast Neoplasms
Triple Negative Breast Neoplasms
Messenger RNA
Neoplasms
nucleolin
Survival
Phase II Clinical Trials
Atlases
Transcriptome

Keywords

  • nucleolin
  • breast cancer
  • prognostic marker
  • triple-negative breast cancer

Cite this

Nguyen Van Long, F., Lardy-Cleaud, A., Bray, S., Chabaud, S., Dubois, T., Diot, A., ... Marcel, V. (2018). Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes. Cancers, 10(10), 1-11. [390]. https://doi.org/10.3390/cancers10100390
Nguyen Van Long, Flora ; Lardy-Cleaud, Audrey ; Bray, Susan ; Chabaud, Sylvie ; Dubois, Thierry ; Diot, Alexandra ; Thompson, Alastair M. ; Bourdon, Jean-Christophe ; Perol, David ; Bouvet, Philippe ; Diaz, Jean-Jacques ; Marcel, Virginie. / Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes. In: Cancers. 2018 ; Vol. 10, No. 10. pp. 1-11.
@article{9aa0bb63ab324e168db60a15eb2b107b,
title = "Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes",
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.",
keywords = "nucleolin, breast cancer, prognostic marker, triple-negative breast cancer",
author = "{Nguyen Van Long}, Flora and Audrey Lardy-Cleaud and Susan Bray and Sylvie Chabaud and Thierry Dubois and Alexandra Diot and Thompson, {Alastair M.} and Jean-Christophe Bourdon and David Perol and Philippe Bouvet and Jean-Jacques Diaz and Virginie Marcel",
note = "Funding: This research was funded by PAIR Sein program (ARC_INCa_LNCC_7625), Fondation ARC (20161204686 and 20171206356) and Ligue Contre le Cancer Comit{\'e}s Allier and Sa{\^o}ne-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 M{\'e}dicale (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).",
year = "2018",
month = "10",
day = "22",
doi = "10.3390/cancers10100390",
language = "English",
volume = "10",
pages = "1--11",
journal = "Cancers",
issn = "2072-6694",
publisher = "MDPI",
number = "10",

}

Nguyen Van Long, F, Lardy-Cleaud, A, Bray, S, Chabaud, S, Dubois, T, Diot, A, Thompson, AM, Bourdon, J-C, Perol, D, Bouvet, P, Diaz, J-J & Marcel, V 2018, 'Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes', Cancers, vol. 10, no. 10, 390, pp. 1-11. https://doi.org/10.3390/cancers10100390

Druggable Nucleolin Identifies Breast Tumours Associated with Poor Prognosis That Exhibit Different Biological Processes. / Nguyen Van Long, Flora; Lardy-Cleaud, Audrey; Bray, Susan; Chabaud, Sylvie; Dubois, Thierry; Diot, Alexandra; Thompson, Alastair M.; Bourdon, Jean-Christophe; Perol, David; Bouvet, Philippe; Diaz, Jean-Jacques (Lead / Corresponding author); Marcel, Virginie (Lead / Corresponding author).

In: Cancers, Vol. 10, No. 10, 390, 22.10.2018, p. 1-11.

Research output: Contribution to journalArticle

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

VL - 10

SP - 1

EP - 11

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 10

M1 - 390

ER -