title: The predictive value of microRNA-126 in relation to first line treatment with capecitabine and oxaliplatin in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  MicroRNA-126 is the only microRNA (miRNA) known to be endothelial cell-specific influencing angiogenesis in several ways. The aim of the present study was to analyse the possible predictive value of miRNA-126 in relation to first line capecitabine and oxaliplatin (XELOX) in patients with metastatic colorectal cancer (mCRC).
  
  
  METHODS
  The study included 89 patients with mCRC. In situ hybridization (ISH) was performed to detect miRNA-126 in formalin-fixed paraffin embedded tissue from primary tumours. The expression of miRNA-126, area per image (μm(2)), was measured using image analysis. Clinical response was evaluated according to RECIST. Progression free survival (PFS) was compared using the Kaplan-Meier method and the log rank test. Tumours were classified as low or high miRNA-126 expressing tumours using the median value from the patients with response as cut-off.
  
  
  RESULTS
  The median miRNA-126 expression level was significantly higher in patients responding to XELOX, 3629 μm(2) (95% CI, 2566-4846), compared to the patients not responding, 1670 μm(2) (95% CI, 1436-2041), p < 0.0001. The positive predictive value was 90%, and the negative predictive value was 71%. The median PFS of patients with high expressing tumours was 11.5 months (95% CI, 9.0-12.7 months) compared to 6.0 months (95% CI, 4.8-6.9 months) for patients with low expressing tumours, p < 0.0001.
  
  
  CONCLUSIONS
  Angiogenesis quantified by ISH of miRNA-126 was related to response to first line XELOX in patients with mCRC, translating to a significant difference in PFS. The predictive value of miRNA-126 remains to be further elucidated in prospective studies.
authors.affiliation: Department of Oncology, Vejle Hospital, Kabbeltoft, Denmark. torben.hansen@slb.regionsyddanmark.dk
authors.forename: Torben Frøstrup
authors.initials: TF
authors.lastname: Hansen
authors.forename: Flemming Brandt
authors.initials: FB
authors.lastname: Sørensen
authors.forename: Jan
authors.initials: J
authors.lastname: Lindebjerg
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000209:etiology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011237:Predictive Value of Tests; D055815:Young Adult
chemical_list: C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil