title: Changes in circulating microRNA-126 during treatment with chemotherapy and bevacizumab predicts treatment response in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  This study investigated the predictive value of circulating microRNA-126 (cir-miRNA-126) in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy combined with bevacizumab.
  
  
  METHODS
  The study included 68 patients. Blood samples (plasma) were collected before the treatment initiation, at the first clinical evaluation after 3 weeks and at progression. Levels of cir-miRNA-126 were determined by qRT-PCR after purification of total RNA from plasma. Primary clinical end points were response rates evaluated according to the Response Evaluation Criteria In Solid Tumours (RECIST) and progression-free survival (PFS).
  
  
  RESULTS
  Changes in circulating miRNA-126 during treatment were predictive of tumour response. Non-responding patients had a median increase in cir-miRNA-126 of 0.244 (95% confidence interval (CI), 0.050-0.565) compared with a median decrease of -0.374 (95% CI, -0.472 to -0.111) in the responding patients, P=0.002. A significant positive correlation was demonstrated by comparing the changes in tumour size with the changes in cir-miRNA-126, r=0.48, P=0.0001. Grouping the patients according to the changes in cir-miRNA-126 disclosed a borderline significant separation of the groups in the PFS analysis favouring patients with decreasing miRNA-126 levels, hazard ratio (HR) 0.60 (95% CI, 0.33-1.09), P=0.07.
  
  
  CONCLUSIONS
  The present results indicate that changes in cir-miRNA-126 during treatment are related to the response to chemotherapy and bevacizumab in patients with mCRC, thus representing a possible biomarker for the resistance to anti-angiogenic containing treatments.
authors.affiliation: 1] Department of Oncology, Vejle Hospital, Part of Lillebaelt Hospital, Vejle, Denmark [2] Institute of Regional Health Research, University of Southern Denmark, Denmark.
authors.forename: T F
authors.initials: TF
authors.lastname: Hansen
authors.affiliation: Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institute, Copenhagen, Denmark.
authors.forename: A L
authors.initials: AL
authors.lastname: Carlsen
authors.affiliation: Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institute, Copenhagen, Denmark.
authors.forename: N H H
authors.initials: NH
authors.lastname: Heegaard
authors.affiliation: 1] Institute of Regional Health Research, University of Southern Denmark, Denmark [2] Department of Clinical Pathology, Vejle Hospital, Part of Lillebaelt Hospital, Vejle, Denmark.
authors.forename: F B
authors.initials: FB
authors.lastname: Sørensen
authors.affiliation: 1] Department of Oncology, Vejle Hospital, Part of Lillebaelt Hospital, Vejle, Denmark [2] Institute of Regional Health Research, University of Southern Denmark, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Jakobsen
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D010071:Oxaloacetates; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D010071:Oxaloacetates; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil