title: Kinome expression profiling and prognosis of basal breast cancers.
abstract: BACKGROUND
  Basal breast cancers (BCs) represent ~15% of BCs. Although overall poor, prognosis is heterogeneous. Identification of good- versus poor-prognosis patients is difficult or impossible using the standard histoclinical features and the recently defined prognostic gene expression signatures (GES). Kinases are often activated or overexpressed in cancers, and constitute targets for successful therapies. We sought to define a prognostic model of basal BCs based on kinome expression profiling.
  
  
  METHODS
  DNA microarray-based gene expression and histoclinical data of 2515 early BCs from thirteen datasets were collected. We searched for a kinome-based GES associated with disease-free survival (DFS) in basal BCs of the learning set using a metagene-based approach. The signature was then tested in basal tumors of the independent validation set.
  
  
  RESULTS
  A total of 591 samples were basal. We identified a 28-kinase metagene associated with DFS in the learning set (N = 73). This metagene was associated with immune response and particularly cytotoxic T-cell response. On multivariate analysis, a metagene-based predictor outperformed the classical prognostic factors, both in the learning and the validation (N = 518) sets, independently of the lymphocyte infiltrate. In the validation set, patients whose tumors overexpressed the metagene had a 78% 5-year DFS versus 54% for other patients (p = 1.62E-4, log-rank test).
  
  
  CONCLUSIONS
  Based on kinome expression, we identified a predictor that separated basal BCs into two subgroups of different prognosis. Tumors associated with higher activation of cytotoxic tumor-infiltrative lymphocytes harbored a better prognosis. Such classification should help tailor the treatment and develop new therapies based on immune response manipulation.
authors.affiliation: Department of Molecular Oncology, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, Institut Paoli-Calmettes, 27 bd Leï Roure, 13009 Marseille, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Sabatier
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Emilie
authors.initials: E
authors.lastname: Mamessier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Raynaud
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cervera
authors.forename: Eric
authors.initials: E
authors.lastname: Lambaudie
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010770:Phosphotransferases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies; D054928:Validation Studies as Topic
chemical_list: D010770:Phosphotransferases