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

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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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Document Type: Research Article

Affiliations: 1: Department of Biochemistry Molecular Biology, Hospices Civils de Lyon (HCL), CHU Lyon Sud, F-69495 Pierre Bénite Cedex, France 2: Department of Oncology Biology, René Gauducheau Cancer Center, F-44805 Nantes - Saint Herblain Cedex, France 3: Department of Oncogenetics, Institut Curie - Hôpital René Huguenin, F-92210 St-Cloud, France 4: Biostatistics Unit, René Gauducheau Cancer Center, F-44805 Nantes - Saint Herblain Cedex, France 5: Department of Medical Oncology, Institut Curie - Hôpital René Huguenin, F-92210 St-Cloud, France 6: Department of Medical Oncology, René Gauducheau Cancer Center, F-44805 Nantes - Saint Herblain Cedex, France 7: Transfer Laboratory of Biological Oncology, AP-HM, Faculty of Medicine North, F-13916 Marseille Cedex 20, France 8: Paul Papin Cancer Center, F-49933 Angers Cedex 9, France 9: Laboratory of Oncology, CORAD, CHU Bretonneau, F-37044 Tours Cedex, France 10: Center for Microanalysis of Proteins, UMS3444 Lyon-Gerland Sud BioSciences, Institute of Biology and Chemistry of Proteins, F-69007 Lyon, France

Publication date: January 1, 2012

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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