title: Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
abstract: OBJECTIVE
  In patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half of treated patients respond to this regimen, and there is no clinically useful marker that predicts response. A major clinical challenge is to identify the subset of patients who could benefit from this chemotherapy. We aimed to identify a gene expression profile in primary colon cancer tissue that could predict chemotherapy response.
  
  
  METHODS
  Tumor colon samples from 21 patients with advanced colorectal cancer were analyzed for gene expression profiling using Human Genome GeneChip arrays U133. At the end of the first-line treatment, the best observed response, according to WHO criteria, was used to define the responders and nonresponders. Discriminatory genes were first selected by the significance analysis of microarrays algorithm and the area under the receiver operating characteristic curve. A predictor classifier was then constructed using support vector machines. Finally, leave-one-out cross validation was used to estimate the performance and the accuracy of the output class prediction rule.
  
  
  RESULTS
  We determined a set of 14 predictor genes of response to FOLFIRI. Nine of nine responders (100% specificity) and 11 of 12 nonresponders (92% sensitivity) were classified correctly, for an overall accuracy of 95%.
  
  
  CONCLUSIONS
  After validation in an independent cohort of patients, our gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting.
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 5160, Service d'Anatomie pathologique, Service d'Oncologie Digestive, Montpellier, France. mdelrio@valdorel.fnclcc.fr
authors.forename: Maguy
authors.initials: M
authors.lastname: Del Rio
authors.forename: Franck
authors.initials: F
authors.lastname: Molina
authors.forename: Caroline
authors.initials: C
authors.lastname: Bascoul-Mollevi
authors.forename: Virginie
authors.initials: V
authors.lastname: Copois
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bibeau
authors.forename: Patrick
authors.initials: P
authors.lastname: Chalbos
authors.forename: Corinne
authors.initials: C
authors.lastname: Bareil
authors.forename: Andrew
authors.initials: A
authors.lastname: Kramar
authors.forename: Nicolas
authors.initials: N
authors.lastname: Salvetat
authors.forename: Caroline
authors.initials: C
authors.lastname: Fraslon
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Conseiller
authors.forename: Virginie
authors.initials: V
authors.lastname: Granci
authors.forename: Benjamin
authors.initials: B
authors.lastname: Leblanc
authors.forename: Bernard
authors.initials: B
authors.lastname: Pau
authors.forename: Pierre
authors.initials: P
authors.lastname: Martineau
authors.forename: Marc
authors.initials: M
authors.lastname: Ychou
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin