title: Absence of transcriptomic signature of response to chemotherapy in metastatic colorectal carcinoma patients.
abstract: OBJECTIVE
  Tumor gene-expression profiling may define signatures capable of discriminating between responders and nonresponders to chemotherapy.
  
  
  METHODS
  Fifty seven metastatic colorectal cancer patients were prospectively included and 40 tumors were analyzed. Patients were treated in first line with 5-fluorouracil associated with irinotecan or oxaliplatin. Response was evaluated using WHO criteria every 2 months after chemotherapy. Gene-expression profiling was performed using Applied Biosystems microarrays (Human Genome Survey Microarray v2.0; Paris, France). Data were analyzed using Bioconductor packages. Differential-expression analysis was performed by fitting a linear model. Moderated t-statistics were computed and p-values were adjusted for false-discovery rate. Pearson correlations tests were evaluated between gene expression and progression-free and overall survival.
  
  
  RESULTS
  Nonsupervised analysis did not show any clustering of expression levels according to treatment response. Supervised analysis compared expression levels between responders and nonresponders, within each treatment group and independently from treatment. No genes were identified as differentially expressed at a p-value of 10(-3) and false-discovery rate of 30%. No correlation between expression levels and survival data was found.
  
  
  CONCLUSIONS
  These negative results show that the determinants of response to chemotherapy should be sought not only in the tumor characteristics, but also among the processes leading to drug availability to the tumor.
authors.affiliation: Institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Laroche-Clary
authors.forename: Audrey
authors.initials: A
authors.lastname: Kauffmann
authors.forename: Denis
authors.initials: D
authors.lastname: Smith
authors.forename: Armelle
authors.initials: A
authors.lastname: Laurand-Quancard
authors.forename: Serge
authors.initials: S
authors.lastname: Evrard
authors.forename: René
authors.initials: R
authors.lastname: Brunet
authors.forename: Valérie
authors.initials: V
authors.lastname: Le Morvan
authors.forename: Jacques
authors.initials: J
authors.lastname: Robert
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin
chemical_list: D054316:Biomarkers, Pharmacological; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin