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


CONCLUSIONS
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.
Department of Oncology, Vejle Hospital, Lillebaelt Hospital, Denmark. torben.hansen@rsyd.dk
T F
TF
Hansen
R dP
Rd
Christensen
R F
RF
Andersen
F B
FB
Sørensen
A
A
Johnsson
A
A
Jakobsen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000235:genetics; D002135:Calcium-Binding Proteins; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D003718:Denmark; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors / Q000378:metabolism*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010071:Oxaloacetates; D020641:Polymorphism, Single Nucleotide; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D013548:Sweden; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D066255:EGF Family of Proteins; C527877:EGFL7 protein, human; D016228:Endothelial Growth Factors; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin