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Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival

BACKGROUND: The development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers f...

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Autores principales: Paiva, Tadeu Ferreira, de Jesus, Victor Hugo Fonseca, Marques, Raul Amorim, da Costa, Alexandre André Balieiro Anastácio, de Macedo, Mariana Petaccia, Peresi, Patricia Maria, Damascena, Aline, Rossi, Benedito Mauro, Begnami, Maria Dirlei, de Lima, Vladmir Cláudio Cordeiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579833/
https://www.ncbi.nlm.nih.gov/pubmed/26394830
http://dx.doi.org/10.1186/s12885-015-1648-4
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author Paiva, Tadeu Ferreira
de Jesus, Victor Hugo Fonseca
Marques, Raul Amorim
da Costa, Alexandre André Balieiro Anastácio
de Macedo, Mariana Petaccia
Peresi, Patricia Maria
Damascena, Aline
Rossi, Benedito Mauro
Begnami, Maria Dirlei
de Lima, Vladmir Cláudio Cordeiro
author_facet Paiva, Tadeu Ferreira
de Jesus, Victor Hugo Fonseca
Marques, Raul Amorim
da Costa, Alexandre André Balieiro Anastácio
de Macedo, Mariana Petaccia
Peresi, Patricia Maria
Damascena, Aline
Rossi, Benedito Mauro
Begnami, Maria Dirlei
de Lima, Vladmir Cláudio Cordeiro
author_sort Paiva, Tadeu Ferreira
collection PubMed
description BACKGROUND: The development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers for anti-angiogenic therapies still exists. METHODS: Clinical data of 105 CRC patients treated with bevacizumab in conjunction with chemotherapy were analyzed. The expression of vascular endothelial growth factor (VEGF) receptors, NOTCH1 receptor and its ligand DLL4 were determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. The association between protein expression and clinicopathological characteristics and outcomes was determined. RESULTS: Bevacizumab was administered as a first-line of treatment in 70.5 % of our cases. The median progression-free survival (PFS) was 10.2 months. The median overall survival (OS) of the total cohort was 24.4 months. Bevacizumab, as the first-line of treatment, and the presence of liver metastasis were independently associated with objective response rate. Membrane VEGFR1 and VEGFR3 expressions were associated with the presence of lung metastasis; interestingly, VEGFR3 was associated with less liver metastasis. NOTCH1 expression was associated with lymph node metastasis. There was a trend toward association between improved PFS and lower NOTCH1 expression (p = 0.06). Improved OS was significantly associated with lower NOTCH1 expression (p = 0.01). In a multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status, liver metastasis, histological grade, and NOTCH1 expression were independently associated with OS. CONCLUSION: Our findings illustrated the expression profile of angiogenesis-related proteins and their association with clinicopathological characteristics and outcomes. NOTCH1 expression is a detrimental prognostic factor in metastatic CRC patients treated with chemotherapy plus bevacizumab. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1648-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-45798332015-09-24 Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival Paiva, Tadeu Ferreira de Jesus, Victor Hugo Fonseca Marques, Raul Amorim da Costa, Alexandre André Balieiro Anastácio de Macedo, Mariana Petaccia Peresi, Patricia Maria Damascena, Aline Rossi, Benedito Mauro Begnami, Maria Dirlei de Lima, Vladmir Cláudio Cordeiro BMC Cancer Research Article BACKGROUND: The development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers for anti-angiogenic therapies still exists. METHODS: Clinical data of 105 CRC patients treated with bevacizumab in conjunction with chemotherapy were analyzed. The expression of vascular endothelial growth factor (VEGF) receptors, NOTCH1 receptor and its ligand DLL4 were determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. The association between protein expression and clinicopathological characteristics and outcomes was determined. RESULTS: Bevacizumab was administered as a first-line of treatment in 70.5 % of our cases. The median progression-free survival (PFS) was 10.2 months. The median overall survival (OS) of the total cohort was 24.4 months. Bevacizumab, as the first-line of treatment, and the presence of liver metastasis were independently associated with objective response rate. Membrane VEGFR1 and VEGFR3 expressions were associated with the presence of lung metastasis; interestingly, VEGFR3 was associated with less liver metastasis. NOTCH1 expression was associated with lymph node metastasis. There was a trend toward association between improved PFS and lower NOTCH1 expression (p = 0.06). Improved OS was significantly associated with lower NOTCH1 expression (p = 0.01). In a multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status, liver metastasis, histological grade, and NOTCH1 expression were independently associated with OS. CONCLUSION: Our findings illustrated the expression profile of angiogenesis-related proteins and their association with clinicopathological characteristics and outcomes. NOTCH1 expression is a detrimental prognostic factor in metastatic CRC patients treated with chemotherapy plus bevacizumab. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1648-4) contains supplementary material, which is available to authorized users. BioMed Central 2015-09-22 /pmc/articles/PMC4579833/ /pubmed/26394830 http://dx.doi.org/10.1186/s12885-015-1648-4 Text en © Paiva et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Paiva, Tadeu Ferreira
de Jesus, Victor Hugo Fonseca
Marques, Raul Amorim
da Costa, Alexandre André Balieiro Anastácio
de Macedo, Mariana Petaccia
Peresi, Patricia Maria
Damascena, Aline
Rossi, Benedito Mauro
Begnami, Maria Dirlei
de Lima, Vladmir Cláudio Cordeiro
Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival
title Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival
title_full Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival
title_fullStr Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival
title_full_unstemmed Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival
title_short Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival
title_sort angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: notch1 detrimental to overall survival
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579833/
https://www.ncbi.nlm.nih.gov/pubmed/26394830
http://dx.doi.org/10.1186/s12885-015-1648-4
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