title: 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.
authors.affiliation: Department of Oncology, Vejle Hospital, part of Lillebaelt Hospital, Vejle, Denmark. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark. torben.hansen@rsyd.dk torbenhansen01@hotmail.com.
authors.forename: Torben Frøstrup
authors.initials: TF
authors.lastname: Hansen
authors.affiliation: Bioneer A/S, Hørsholm, Denmark.
authors.forename: Boye Schnack
authors.initials: BS
authors.lastname: Nielsen
authors.affiliation: Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark. Department of Clinical Pathology, Vejle Hospital, Part of Lillebaelt Hospital, Vejle, Denmark.
authors.forename: Flemming Brandt
authors.initials: FB
authors.lastname: Sørensen
authors.affiliation: Department of Oncology, University Hospital, Lund, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Johnsson
authors.affiliation: Department of Oncology, Vejle Hospital, part of Lillebaelt Hospital, Vejle, Denmark. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000737:chemistry; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000737:chemistry*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002135:Calcium-Binding Proteins; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018572:Disease-Free Survival; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D057170:Translational Research, Biomedical; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D066255:EGF Family of Proteins; C527877:EGFL7 protein, human; D016228:Endothelial Growth Factors; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D000068258:Bevacizumab