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

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...

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Autores principales: Zuurbier, Linda, Rahman, Arman, Cordes, Martijn, Scheick, Jennifer, Wong, Tse J., Rustenburg, François, Joseph, Jesu Christopher, Dynoodt, Peter, Casey, Rory, Drillenburg, Paul, Gerhards, Michael, Barat, Ana, Klinger, Rut, Fender, Bozena, O’Connor, Darran P., Betge, Johannes, Ebert, Matthias P., Gaiser, Timo, Prehn, Jochen H. M., Griffioen, Arjan W., van Grieken, Nicole C. T., Ylstra, Bauke, Byrne, Annette T., van der Flier, Laurens G., Gallagher, William M., Postel, Ruben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522118/
https://www.ncbi.nlm.nih.gov/pubmed/28487489
http://dx.doi.org/10.18632/oncotarget.17306
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author Zuurbier, Linda
Rahman, Arman
Cordes, Martijn
Scheick, Jennifer
Wong, Tse J.
Rustenburg, François
Joseph, Jesu Christopher
Dynoodt, Peter
Casey, Rory
Drillenburg, Paul
Gerhards, Michael
Barat, Ana
Klinger, Rut
Fender, Bozena
O’Connor, Darran P.
Betge, Johannes
Ebert, Matthias P.
Gaiser, Timo
Prehn, Jochen H. M.
Griffioen, Arjan W.
van Grieken, Nicole C. T.
Ylstra, Bauke
Byrne, Annette T.
van der Flier, Laurens G.
Gallagher, William M.
Postel, Ruben
author_facet Zuurbier, Linda
Rahman, Arman
Cordes, Martijn
Scheick, Jennifer
Wong, Tse J.
Rustenburg, François
Joseph, Jesu Christopher
Dynoodt, Peter
Casey, Rory
Drillenburg, Paul
Gerhards, Michael
Barat, Ana
Klinger, Rut
Fender, Bozena
O’Connor, Darran P.
Betge, Johannes
Ebert, Matthias P.
Gaiser, Timo
Prehn, Jochen H. M.
Griffioen, Arjan W.
van Grieken, Nicole C. T.
Ylstra, Bauke
Byrne, Annette T.
van der Flier, Laurens G.
Gallagher, William M.
Postel, Ruben
author_sort Zuurbier, Linda
collection PubMed
description 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.
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spelling pubmed-55221182017-08-08 Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer Zuurbier, Linda Rahman, Arman Cordes, Martijn Scheick, Jennifer Wong, Tse J. Rustenburg, François Joseph, Jesu Christopher Dynoodt, Peter Casey, Rory Drillenburg, Paul Gerhards, Michael Barat, Ana Klinger, Rut Fender, Bozena O’Connor, Darran P. Betge, Johannes Ebert, Matthias P. Gaiser, Timo Prehn, Jochen H. M. Griffioen, Arjan W. van Grieken, Nicole C. T. Ylstra, Bauke Byrne, Annette T. van der Flier, Laurens G. Gallagher, William M. Postel, Ruben Oncotarget Research Paper 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. Impact Journals LLC 2017-04-21 /pmc/articles/PMC5522118/ /pubmed/28487489 http://dx.doi.org/10.18632/oncotarget.17306 Text en Copyright: © 2017 Zuurbier et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Zuurbier, Linda
Rahman, Arman
Cordes, Martijn
Scheick, Jennifer
Wong, Tse J.
Rustenburg, François
Joseph, Jesu Christopher
Dynoodt, Peter
Casey, Rory
Drillenburg, Paul
Gerhards, Michael
Barat, Ana
Klinger, Rut
Fender, Bozena
O’Connor, Darran P.
Betge, Johannes
Ebert, Matthias P.
Gaiser, Timo
Prehn, Jochen H. M.
Griffioen, Arjan W.
van Grieken, Nicole C. T.
Ylstra, Bauke
Byrne, Annette T.
van der Flier, Laurens G.
Gallagher, William M.
Postel, Ruben
Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer
title Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer
title_full Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer
title_fullStr Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer
title_full_unstemmed Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer
title_short Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer
title_sort apelin: a putative novel predictive biomarker for bevacizumab response in colorectal cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522118/
https://www.ncbi.nlm.nih.gov/pubmed/28487489
http://dx.doi.org/10.18632/oncotarget.17306
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