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VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer

Bevacizumab is used to treat metastatic colorectal cancer (mCRC). However, there are still no available predictors of clinical outcomes. We investigated selected single nucleotide polymorphisms (SNPs) in the genes involved in VEGF-dependent and -independent angiogenesis pathways and other major intr...

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Autores principales: Papachristos, Apostolos, Kemos, Polychronis, Katsila, Theodora, Panoilia, Eirini, Patrinos, George P., Kalofonos, Haralabos, Sivolapenko, Gregory B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888109/
https://www.ncbi.nlm.nih.gov/pubmed/31752122
http://dx.doi.org/10.3390/ijms20225791
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author Papachristos, Apostolos
Kemos, Polychronis
Katsila, Theodora
Panoilia, Eirini
Patrinos, George P.
Kalofonos, Haralabos
Sivolapenko, Gregory B.
author_facet Papachristos, Apostolos
Kemos, Polychronis
Katsila, Theodora
Panoilia, Eirini
Patrinos, George P.
Kalofonos, Haralabos
Sivolapenko, Gregory B.
author_sort Papachristos, Apostolos
collection PubMed
description Bevacizumab is used to treat metastatic colorectal cancer (mCRC). However, there are still no available predictors of clinical outcomes. We investigated selected single nucleotide polymorphisms (SNPs) in the genes involved in VEGF-dependent and -independent angiogenesis pathways and other major intracellular signaling pathways involved in the pathogenesis of mCRC as an attempt to find predictors of clinical outcome. Forty-six patients treated with first-line bevacizumab-based chemotherapy were included in this study with a 5 year follow up. Genomic DNA was isolated from whole blood for the analysis of VEGF-A (rs2010963, 1570360, rs699947), ICAM-1 (rs5498, rs1799969) SNPs and from tumor tissue for the detection of genomic variants in KRAS, NRAS, BRAF genes. PCR and next generation sequencing were used for the analysis. The endpoints of the study were progression-free survival (PFS) and overall survival (OS). The VEGF-A rs699947 A/A allele was associated with increased PFS (p = 0.006) and OS (p = 0.043). The ICAM-1 rs1799969 G/A allele was associated with prolonged OS (p = 0.036). Finally, BRAF wild type was associated with increased OS (p = 0.027). We identified VEGF-A and ICAM-1 variants in angiogenesis and other major intracellular signaling pathways, such as BRAF, that can predict clinical outcome upon bevacizumab administration. These identified biomarkers could be used to select patients with mCRC who may achieve long-term responses and benefit from bevacizumab-based therapies.
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spelling pubmed-68881092019-12-09 VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer Papachristos, Apostolos Kemos, Polychronis Katsila, Theodora Panoilia, Eirini Patrinos, George P. Kalofonos, Haralabos Sivolapenko, Gregory B. Int J Mol Sci Article Bevacizumab is used to treat metastatic colorectal cancer (mCRC). However, there are still no available predictors of clinical outcomes. We investigated selected single nucleotide polymorphisms (SNPs) in the genes involved in VEGF-dependent and -independent angiogenesis pathways and other major intracellular signaling pathways involved in the pathogenesis of mCRC as an attempt to find predictors of clinical outcome. Forty-six patients treated with first-line bevacizumab-based chemotherapy were included in this study with a 5 year follow up. Genomic DNA was isolated from whole blood for the analysis of VEGF-A (rs2010963, 1570360, rs699947), ICAM-1 (rs5498, rs1799969) SNPs and from tumor tissue for the detection of genomic variants in KRAS, NRAS, BRAF genes. PCR and next generation sequencing were used for the analysis. The endpoints of the study were progression-free survival (PFS) and overall survival (OS). The VEGF-A rs699947 A/A allele was associated with increased PFS (p = 0.006) and OS (p = 0.043). The ICAM-1 rs1799969 G/A allele was associated with prolonged OS (p = 0.036). Finally, BRAF wild type was associated with increased OS (p = 0.027). We identified VEGF-A and ICAM-1 variants in angiogenesis and other major intracellular signaling pathways, such as BRAF, that can predict clinical outcome upon bevacizumab administration. These identified biomarkers could be used to select patients with mCRC who may achieve long-term responses and benefit from bevacizumab-based therapies. MDPI 2019-11-18 /pmc/articles/PMC6888109/ /pubmed/31752122 http://dx.doi.org/10.3390/ijms20225791 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Papachristos, Apostolos
Kemos, Polychronis
Katsila, Theodora
Panoilia, Eirini
Patrinos, George P.
Kalofonos, Haralabos
Sivolapenko, Gregory B.
VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer
title VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer
title_full VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer
title_fullStr VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer
title_full_unstemmed VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer
title_short VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer
title_sort vegf-a and icam-1 gene polymorphisms as predictors of clinical outcome to first-line bevacizumab-based treatment in metastatic colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888109/
https://www.ncbi.nlm.nih.gov/pubmed/31752122
http://dx.doi.org/10.3390/ijms20225791
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