title: Clinical Impact of a Novel MicroRNA Chemo-Sensitivity Predictor in Gastrooesophageal Cancer.
abstract: BACKGROUND
  miRNAs might be potentially useful biomarkers for prediction of response to chemotherapeutic agents, radiotherapy and survival. The aim of this retrospective study was to validate miRNA response predictors in a cohort of patients with gastrooesophageal cancer in order to predict overall survival (OS) and disease-specific survival (DSS).
  
  
  METHODS
  The study population encompassed 53 patients treated with curative intend for loco-regional gastrooesophageal cancer. miRNA expression was quantified from pre-therapeutic and diagnostic, formalin-fixed, paraffin embedded tumour specimens using Affymetrix GeneChip miRNA 1.0 Array. Based on growth inhibition of the NCI60 panel in the presence of cisplatin, epirubicine and capecitabine, a miRNA based response predictor was developed. The Cox proportional hazards model was applied to assess the correlations of the response predictor with OS and DSS.
  
  
  RESULTS
  A univariate analysis demonstrated a statistical significant improvement of OS for patients who had undergone surgical resection with prediction scores above the median prediction score (HR: 0.41 (95% CI: 0.17-0.96). Adjusting for surgery and stage, this predictor was identified to be independently associated with both OS (HR: 0.37 (95% CI: 0.16-0.87)) and DSS (HR: 0.32 (0.12-0.87)).
  
  
  CONCLUSIONS
  The miRNA profile predictive for sensitivity to cisplatin, epirubicine and capecitabine was shown to be independently associated with OS and DSS in patients with gastrooesophageal cancer.
authors.affiliation: Dept. of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Winther
authors.affiliation: Medical Prognosis Institute, Hoersholm, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Knudsen
authors.affiliation: Centre for Health Promotion and Rehabilitation, Faculty of Health Sciences, VIA University College, Aarhus, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Dahlgaard
authors.affiliation: Medical Prognosis Institute, Hoersholm, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jensen
authors.affiliation: Medical Prognosis Institute, Hoersholm, Denmark.
authors.forename: Anker
authors.initials: A
authors.lastname: Hansen
authors.affiliation: Medical Prognosis Institute, Hoersholm, Denmark.
authors.forename: Peter Buhl
authors.initials: PB
authors.lastname: Jensen
authors.affiliation: Dept. of Pathology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Tramm
authors.affiliation: Dept. of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Alsner
authors.affiliation: Dept. of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Nordsmark
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs