Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis: A multicentric 2004 national PHRC study

  • Authors:
    • Françoise Descotes
    • Pascal Jézéquel
    • Frédérique Spyratos
    • Loïc Campion
    • Catherine Grenot
    • Florence Lerebours
    • Mario Campone
    • Catherine Guérin-Charbonnel
    • Didier Lanoë
    • Marjorie Adams
    • Jean André
    • Antoine Carlioz
    • Pierre-Marie Martin
    • Agnès Chassevent
    • Marie-Lise Jourdan
    • Catherine Guette
    • Isabelle Zanella-Cleon
    • Gabriel Ricolleau
  • View Affiliations

  • Published online on: April 30, 2012     https://doi.org/10.3892/ijo.2012.1456
  • Pages: 92-104
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Abstract

We used a 2D-electrophoresis (2-DE) proteomic approach to identify novel biomarkers in node-negative breast cancers. This retrospective study focused on a population of patients with ductal pN0M0 tumours. A subset of patients who developed metastases and in whose tumours were found high levels of uPA and PAI-1 (metastatic relapse, MR: n=20) were compared to another subset in whom no metastatic relapse occurred and whose tumours were found to have low levels of uPA and PAI-1 (no relapse, NR: n=21). We used a 2-DE coupled with MS approach to screen cytosol fractions using two pH-gradient scales, a broad scale (3.0-11.0) and a narrower scale focussing in on a protein rich region (5.0-8.0). This study was conducted on 41 cytosol specimens analyzed in duplicate on two platforms. The differential analysis of more than 2,000 spots in 2-DE gels, obtained on the two platforms, allowed the identification of 13 proteins which were confirmed by western blotting. Two proteins, GPDA and FABP4 were down-regulated in the MR subset whereas all the others were up-regulated. An in silico analysis revealed that GMPS (GUAA), GAPDH (G3P), CFL1 (COF1) and FTL (FRIL), the most informative genes, displayed a proliferation profile (high expression in basal-like, HER2+ and luminal B molecular subtypes). Inversely, similar to FABP4, GPD1 [GPDA] displayed a high expression in luminal A subtype, a profile characteristic of tumour suppressor genes. Despite the small size of our cohort, the 2-DE analysis gave interesting results which were confirmed by the in silico analysis showing that some of the corresponding genes had a strong prognostic impact in breast cancer, mostly because of their link with proliferation: GMPS, GAPDH, FTL and GPD1. A validation phase on a larger cohort is now needed before these biomarkers could be considered for use in clinical practice.

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July 2012
Volume 41 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Descotes F, Jézéquel P, Spyratos F, Campion L, Grenot C, Lerebours F, Campone M, Guérin-Charbonnel C, Lanoë D, Adams M, Adams M, et al: Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis: A multicentric 2004 national PHRC study. Int J Oncol 41: 92-104, 2012
APA
Descotes, F., Jézéquel, P., Spyratos, F., Campion, L., Grenot, C., Lerebours, F. ... Ricolleau, G. (2012). Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis: A multicentric 2004 national PHRC study. International Journal of Oncology, 41, 92-104. https://doi.org/10.3892/ijo.2012.1456
MLA
Descotes, F., Jézéquel, P., Spyratos, F., Campion, L., Grenot, C., Lerebours, F., Campone, M., Guérin-Charbonnel, C., Lanoë, D., Adams, M., André, J., Carlioz, A., Martin, P., Chassevent, A., Jourdan, M., Guette, C., Zanella-Cleon, I., Ricolleau, G."Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis: A multicentric 2004 national PHRC study". International Journal of Oncology 41.1 (2012): 92-104.
Chicago
Descotes, F., Jézéquel, P., Spyratos, F., Campion, L., Grenot, C., Lerebours, F., Campone, M., Guérin-Charbonnel, C., Lanoë, D., Adams, M., André, J., Carlioz, A., Martin, P., Chassevent, A., Jourdan, M., Guette, C., Zanella-Cleon, I., Ricolleau, G."Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis: A multicentric 2004 national PHRC study". International Journal of Oncology 41, no. 1 (2012): 92-104. https://doi.org/10.3892/ijo.2012.1456