title: MiR-320e is a novel prognostic biomarker in colorectal cancer.
abstract: BACKGROUND
  Advances in early detection and treatment have improved outcomes in patients with colorectal cancer (CRC). However, there remains a need for robust prognostic and predictive biomarkers. We conducted a systematic discovery and validation of microRNA (miRNA) biomarkers in two clinical trial cohorts of CRC patients.
  
  
  METHODS
  We performed an initial 'discovery' phase using Affymetrix miRNA expression arrays to profile stage III CRC patients with and without tumour recurrence (n=50 per group) at 3-years of follow-up. All patients received adjuvant 5-fluorouracil (5-FU) plus oxaliplatin, that is, FOLFOX, treatment. During 'validation', we analysed miRNAs using qRT-PCR in an independent cohort of 237 stage II-IV CRC patients treated with 5-FU-based chemotherapy, as well as in normal colonic mucosa from 20 healthy subjects. Association with disease recurrence, disease-free survival (DFS) and overall survival (OS) was examined using Cox proportional hazard models.
  
  
  RESULTS
  In the discovery cohort, miR-320e expression was significantly elevated in stage III colon cancers from patients with vs without recurrence (95% confidence interval (CI)=1.14-1.42; P<0.0001). These results were then independently validated in stage II and III tumours. Specifically, increased miR-320e expression was associated with poorer DFS (hazard ratio (HR)=1.65; 95% CI=1.27-2.13; P=0.0001) and OS (HR=1.78; 95% CI=1.31-2.41; P=0.0003) in stage III CRC patients.
  
  
  CONCLUSIONS
  In two clinical trial cohorts, a systematic biomarker discovery and validation approach identified miR-320e to be a novel prognostic biomarker that is associated with adverse clinical outcome in stage III CRC patients treated with 5-FU-based adjuvant chemotherapy. These findings have important implications for the personalised management of CRC patients.
authors.affiliation: Center for Gastrointestinal Research; Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute, Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Perez-Carbonell
authors.affiliation: 1] Division of Oncology, Mayo Clinic, Rochester, MN, USA [2] Division Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: F A
authors.initials: FA
authors.lastname: Sinicrope
authors.affiliation: 1] Division of Oncology, Mayo Clinic, Rochester, MN, USA [2] Division Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Alberts
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Oberg
authors.affiliation: Department of Gastroenterology, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Balaguer
authors.affiliation: Department of Gastroenterology, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Castells
authors.affiliation: Center for Gastrointestinal Research; Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute, Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Boland
authors.affiliation: Center for Gastrointestinal Research; Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute, Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Goel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil