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Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer.

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journal contribution
posted on 22.11.2019, 16:51 authored by Linda Zuurbier, Arman Rahman, Martijn Cordes, Jennifer Scheick, Tse J. Wong, François Rustenburg, Jesu C. Joseph, Peter Dynoodt, Rory Casey, Paul Drillenburg, Michael Gerhards, Ana Barat, Rut Klinger, Bozena Fender, Darran P. O'Connor, Johannes Betge, Matthias P. Ebert, Timo Gaiser, Jochen HM Prehn, Arjan W. Griffioen, Nicole CT van Grieken, Bauke Ylstra, Annette Byrne, Laurens G. van der Flier, William M. Gallagher, Ruben Postel

Bevacizumab (bvz) is currently employed as an anti-angiogenic therapy across several cancer indications. Bvz response heterogeneity has been well documented, with only 10-15% of colorectal cancer (CRC) patients benefitting in general. For other patients, clinical efficacy is limited and side effects are significant. This reinforces the need for a robust predictive biomarker of response. To identify such a biomarker, we performed a DNA microarray-based transcriptional profiling screen with primary endothelial cells (ECs) isolated from normal and tumour colon tissues. Thirteen separate populations of tumour-associated ECs and 10 of normal ECs were isolated using fluorescence-activated cell sorting. We hypothesised that VEGF-induced genes were overexpressed in tumour ECs; these genes could relate to bvz response and serve as potential predictive biomarkers. Transcriptional profiling revealed a total of 2,610 differentially expressed genes when tumour and normal ECs were compared. To explore their relation to bvz response, the mRNA expression levels of top-ranked genes were examined using quantitative PCR in 30 independent tumour tissues from CRC patients that received bvz in the adjuvant setting. These analyses revealed that the expression of MMP12 and APLN mRNA was significantly higher in bvz non-responders compared to responders. At the protein level, high APLN expression was correlated with poor progression-free survival in bvz-treated patients. Thus, high APLN expression may represent a novel predictive biomarker for bvz unresponsiveness.


This work was financially supported by the European Commission’s Seventh Framework Programme (FP7) under contract No.278981 (ANGIOPREDICT).



The original article is available at http://www.oncotarget.com

Published Citation

Zuurbier L, Rahman A, Cordes M, Scheick J, Wong TJ, Rustenburg F, et al. Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer. Oncotarget. 2017;8(26):42949-42961

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