MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial

Br J Cancer. 2013 Sep 3;109(5):1243-51. doi: 10.1038/bjc.2013.448. Epub 2013 Aug 6.

Abstract

Background: This study investigated the clinical importance of linked angiogenetic biomarkers to chemotherapy, combined with the anti-vascular endothelial growth factor A (anti-VEGF-A), as a first-line treatment in patients with metastatic colorectal cancer (mCRC).

Methods: A total of 230 patients from a randomised phase III study were included. The primary microRNA-126 (pri-miRNA-126) A24G single-nucleotide polymorphism and the mature miRNA-126 were analysed by PCR using genomic DNA (full blood) and formalin-fixed paraffin-embedded tissue sections, respectively. The epidermal growth factor-like domain 7 (EGFL7) protein was visualised and quantified using immunohistochemistry.

Results: High tumour expression of miRNA-126 was significantly related to a longer progression-free survival. The independent prognostic value of miRNA-126 was confirmed using a Cox regression analysis (hazard ratio=0.49, 95% confidence interval=0.29-0.84, P=0.009). Although not significant, a relationship between EGFL7 expression and response rates is suggested, with EGFL7 expression at the invasive front being lower in responding patients than in the non-responders (P=0.063).

Conclusion: The results validate the previous findings on the prognostic value of miRNA-126 in mCRC and may suggest a relationship between treatment efficacy and EGFL7 expression. As miRNA-126 may target VEGF-A as well as EGFL7, the results may provide predictive information in relation to next-generation anti-angiogenetics.

Trial registration: ClinicalTrials.gov NCT00598156.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Biomarkers, Tumor / genetics
  • Calcium-Binding Proteins
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Capecitabine
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Dänemark
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • EGF Family of Proteins
  • Endothelial Growth Factors / metabolism*
  • ErbB Receptors / antagonists & inhibitors
  • Erlotinib Hydrochloride
  • Female
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neovascularization, Pathologic / drug therapy
  • Organoplatinum Compounds / therapeutic use
  • Oxaloacetates
  • Polymorphism, Single Nucleotide
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines / therapeutic use
  • Schweden
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • EGF Family of Proteins
  • EGFL7 protein, human
  • Endothelial Growth Factors
  • MIRN126 microRNA, human
  • MicroRNAs
  • Organoplatinum Compounds
  • Oxaloacetates
  • Protein Kinase Inhibitors
  • Quinazolines
  • Vascular Endothelial Growth Factor A
  • Deoxycytidine
  • Bevacizumab
  • Capecitabine
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Folfox protocol
  • IFL protocol
  • XELOX

Associated data

  • ClinicalTrials.gov/NCT00598156