title: Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis: a multicentric 2004 national PHRC study.
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.
authors.affiliation: Department of Biochemistry Molecular Biology, Hospices Civils de Lyon, CHU Lyon Sud, F-69495 Pierre Bénite Cedex, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Descotes
authors.forename: Pascal
authors.initials: P
authors.lastname: Jézéquel
authors.forename: Frédérique
authors.initials: F
authors.lastname: Spyratos
authors.forename: Loïc
authors.initials: L
authors.lastname: Campion
authors.forename: Catherine
authors.initials: C
authors.lastname: Grenot
authors.forename: Florence
authors.initials: F
authors.lastname: Lerebours
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Catherine
authors.initials: C
authors.lastname: Guérin-Charbonnel
authors.forename: Didier
authors.initials: D
authors.lastname: Lanoë
authors.forename: Marjorie
authors.initials: M
authors.lastname: Adams
authors.forename: Jean
authors.initials: J
authors.lastname: André
authors.forename: Antoine
authors.initials: A
authors.lastname: Carlioz
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Martin
authors.forename: Agnès
authors.initials: A
authors.lastname: Chassevent
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Jourdan
authors.forename: Catherine
authors.initials: C
authors.lastname: Guette
authors.forename: Isabelle
authors.initials: I
authors.lastname: Zanella-Cleon
authors.forename: Gabriel
authors.initials: G
authors.lastname: Ricolleau
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015870:Gene Expression; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010449:Peptide Mapping; D011379:Prognosis; D040901:Proteomics; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D010446:Peptide Fragments