title: The prognostic role of a gene signature from tumorigenic breast-cancer cells.
abstract: BACKGROUND
  Breast cancers contain a minority population of cancer cells characterized by CD44 expression but low or undetectable levels of CD24 (CD44+CD24-/low) that have higher tumorigenic capacity than other subtypes of cancer cells.
  
  
  METHODS
  We compared the gene-expression profile of CD44+CD24-/low tumorigenic breast-cancer cells with that of normal breast epithelium. Differentially expressed genes were used to generate a 186-gene "invasiveness" gene signature (IGS), which was evaluated for its association with overall survival and metastasis-free survival in patients with breast cancer or other types of cancer.
  
  
  RESULTS
  There was a significant association between the IGS and both overall and metastasis-free survival (P<0.001, for both) in patients with breast cancer, which was independent of established clinical and pathological variables. When combined with the prognostic criteria of the National Institutes of Health, the IGS was used to stratify patients with high-risk early breast cancer into prognostic categories (good or poor); among patients with a good prognosis, the 10-year rate of metastasis-free survival was 81%, and among those with a poor prognosis, it was 57%. The IGS was also associated with the prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). The prognostic power of the IGS was increased when combined with the wound-response (WR) signature.
  
  
  CONCLUSIONS
  The IGS is strongly associated with metastasis-free survival and overall survival for four different types of tumors. This genetic signature of tumorigenic breast-cancer cells was even more strongly associated with clinical outcomes when combined with the WR signature in breast cancer.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Xinhao
authors.initials: X
authors.lastname: Wang
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Chen
authors.forename: Piero
authors.initials: P
authors.lastname: Dalerba
authors.forename: Austin
authors.initials: A
authors.lastname: Gurney
authors.forename: Timothy
authors.initials: T
authors.lastname: Hoey
authors.forename: Gavin
authors.initials: G
authors.lastname: Sherlock
authors.forename: John
authors.initials: J
authors.lastname: Lewicki
authors.forename: Kerby
authors.initials: K
authors.lastname: Shedden
authors.forename: Michael F
authors.initials: MF
authors.lastname: Clarke
mesh_terms: D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D051927:CD24 Antigen; D004848:Epithelium; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018960:Hyaluronan Receptors; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality; D008297:Male; D008527:Medulloblastoma / Q000235:genetics / Q000401:mortality; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000401:mortality
chemical_list: D051927:CD24 Antigen; D018960:Hyaluronan Receptors