Epidermal growth factor-like domain 7 predicts response to first-line chemotherapy and bevacizumab in patients with metastatic colorectal cancer.

Abstract:

:The number of approved antiangiogenic drugs is constantly growing and emphasizes the need for predictive biomarkers. The aim of this study was to analyze the predictive value of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126 (miR126) to first-line chemotherapy combined with bevacizumab, in patients with metastatic colorectal cancer (mCRC). A total of 158 patients from two different, but comparable, cohorts were included. Analyses were performed on tumor tissue from the primary tumor either based on a whole-tumor resection or an endoscopic biopsy. EGFL7 was analyzed by immunohistochemistry (IHC) and miR126 by in situ hybridization (ISH). Both biomarkers were quantified by image-guided analyses. Endpoints were response rate (RR) and progression-free survival (PFS). The EGFL7 vessel area (VA) in tumor resections was closely related to treatment response with a median EGFL7 VA in responding patients of 4 [95% confidence interval (CI), 4-6] compared with 8.5 (95% CI, 7-11) in nonresponders, P = 0.0008. This difference translated into a borderline significant difference in PFS (P = 0.06). Furthermore, a significant relationship between high EGFL7 VA and KRAS mutation was detected (P = 0.049). The results showed no significant relationship between the miR126 VA and the clinical endpoints. Our study suggests a predictive value of EGFL7 in regard to first-line chemotherapy and bevacizumab in patients with mCRC and supports the mechanism of a dual blocking of the vascular endothelial growth factor-A and EGFL7 axis in this setting.

journal_name

Mol Cancer Ther

authors

Hansen TF,Nielsen BS,Sørensen FB,Johnsson A,Jakobsen A

doi

10.1158/1535-7163.MCT-14-0131

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

2238-45

issue

9

eissn

1535-7163

issn

1538-8514

pii

1535-7163.MCT-14-0131

journal_volume

13

pub_type

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