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Open Access Highly Accessed Research article

The predictive value of microRNA-126 in relation to first line treatment with capecitabine and oxaliplatin in patients with metastatic colorectal cancer

Torben Frøstrup Hansen13*, Flemming Brandt Sørensen2, Jan Lindebjerg2 and Anders Jakobsen1

Author Affiliations

1 Department of Oncology, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark

2 Department of Clinical Pathology, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark

3 Danish Colorectal Cancer Group South, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark

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BMC Cancer 2012, 12:83  doi:10.1186/1471-2407-12-83

Published: 8 March 2012

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 (μm2), 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 μm2 (95% CI, 2566-4846), compared to the patients not responding, 1670 μm2 (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.

Keywords:
Angiogenesis; Chemotherapy; Colorectal neoplasms; microRNAs; Predictive biomarkers