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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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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. |
format | Online Article Text |
id | pubmed-5522118 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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