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Br J Cancer ; 109(5): 1243-51, 2013 Sep 03.
Article in English | MEDLINE | ID: mdl-23922111

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.


Subject(s)
Colorectal Neoplasms/drug therapy , Endothelial Growth Factors/metabolism , MicroRNAs/metabolism , 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/metabolism , Colorectal Neoplasms/mortality , Denmark , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Disease-Free Survival , EGF Family of Proteins , ErbB Receptors/antagonists & inhibitors , Erlotinib Hydrochloride , Female , Fluorouracil/analogs & derivatives , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Male , MicroRNAs/genetics , Middle Aged , Neovascularization, Pathologic/drug therapy , Organoplatinum Compounds/therapeutic use , Oxaloacetates , Polymorphism, Single Nucleotide , Protein Kinase Inhibitors/therapeutic use , Quinazolines/therapeutic use , Sweden , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitors
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