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KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study

KRAS mutation is a confirmed predictive biomarker for anti-EGFR monoclonal antibody therapy response for metastatic colorectal cancer. However, its prognosis impact and the predictive potential for first-line standard chemotherapy remains unclear. On the other hand, V600E mutation is the most freque...

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Autores principales: Garcia-Carbonero, Nuria, Martinez-Useros, Javier, Li, Weiyao, Orta, Alberto, Perez, Nuria, Carames, Cristina, Hernandez, Tatiana, Moreno, Irene, Serrano, Gloria, Garcia-Foncillas, Jesus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016634/
https://www.ncbi.nlm.nih.gov/pubmed/31952366
http://dx.doi.org/10.3390/cells9010219
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author Garcia-Carbonero, Nuria
Martinez-Useros, Javier
Li, Weiyao
Orta, Alberto
Perez, Nuria
Carames, Cristina
Hernandez, Tatiana
Moreno, Irene
Serrano, Gloria
Garcia-Foncillas, Jesus
author_facet Garcia-Carbonero, Nuria
Martinez-Useros, Javier
Li, Weiyao
Orta, Alberto
Perez, Nuria
Carames, Cristina
Hernandez, Tatiana
Moreno, Irene
Serrano, Gloria
Garcia-Foncillas, Jesus
author_sort Garcia-Carbonero, Nuria
collection PubMed
description KRAS mutation is a confirmed predictive biomarker for anti-EGFR monoclonal antibody therapy response for metastatic colorectal cancer. However, its prognosis impact and the predictive potential for first-line standard chemotherapy remains unclear. On the other hand, V600E mutation is the most frequent and studied mutation in the BRAF gene, and it has been associated with a poor outcome of patients and a low response to anti-EGFR treatment. Thus, the aim of this study is to evaluate the role of KRAS and BRAF mutations as prognosis factors and predictive biomarkers for 1st line standard chemotherapy in metastatic colorectal cancer. KRAS mutations and BRAF V600E mutations exhibited a poor outcome (p = 0.021 and p < 0.0001, respectively). Cox multivariate analysis showed that the presence of liver metastasis (HR = 1.595; 95% CI: 1.086–2.343; p = 0.017), KRAS mutation (HR = 1.643; 95% CI: 1.110–2.431; p = 0.013) and BRAF V600E mutation (HR = 5.861; 95% CI: 2.531–13.570; p < 0.0001) were statistically significant co-variables for progression-free survival. Interestingly, patients with KRAS mutations were associated with a poor response to first line standard chemotherapy (p = 0.008). In contrast, the BRAF V600E mutation did not have any impact on the first line standard chemotherapy response (p = 0.540). Therefore, in the present study, we provide new insight on the role of KRAS and BRAF, not only as prognosis biomarkers, but also as first line standard chemotherapy response biomarkers in metastatic colorectal cancer.
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spelling pubmed-70166342020-03-04 KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study Garcia-Carbonero, Nuria Martinez-Useros, Javier Li, Weiyao Orta, Alberto Perez, Nuria Carames, Cristina Hernandez, Tatiana Moreno, Irene Serrano, Gloria Garcia-Foncillas, Jesus Cells Article KRAS mutation is a confirmed predictive biomarker for anti-EGFR monoclonal antibody therapy response for metastatic colorectal cancer. However, its prognosis impact and the predictive potential for first-line standard chemotherapy remains unclear. On the other hand, V600E mutation is the most frequent and studied mutation in the BRAF gene, and it has been associated with a poor outcome of patients and a low response to anti-EGFR treatment. Thus, the aim of this study is to evaluate the role of KRAS and BRAF mutations as prognosis factors and predictive biomarkers for 1st line standard chemotherapy in metastatic colorectal cancer. KRAS mutations and BRAF V600E mutations exhibited a poor outcome (p = 0.021 and p < 0.0001, respectively). Cox multivariate analysis showed that the presence of liver metastasis (HR = 1.595; 95% CI: 1.086–2.343; p = 0.017), KRAS mutation (HR = 1.643; 95% CI: 1.110–2.431; p = 0.013) and BRAF V600E mutation (HR = 5.861; 95% CI: 2.531–13.570; p < 0.0001) were statistically significant co-variables for progression-free survival. Interestingly, patients with KRAS mutations were associated with a poor response to first line standard chemotherapy (p = 0.008). In contrast, the BRAF V600E mutation did not have any impact on the first line standard chemotherapy response (p = 0.540). Therefore, in the present study, we provide new insight on the role of KRAS and BRAF, not only as prognosis biomarkers, but also as first line standard chemotherapy response biomarkers in metastatic colorectal cancer. MDPI 2020-01-15 /pmc/articles/PMC7016634/ /pubmed/31952366 http://dx.doi.org/10.3390/cells9010219 Text en © 2020 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
Garcia-Carbonero, Nuria
Martinez-Useros, Javier
Li, Weiyao
Orta, Alberto
Perez, Nuria
Carames, Cristina
Hernandez, Tatiana
Moreno, Irene
Serrano, Gloria
Garcia-Foncillas, Jesus
KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study
title KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study
title_full KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study
title_fullStr KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study
title_full_unstemmed KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study
title_short KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study
title_sort kras and braf mutations as prognostic and predictive biomarkers for standard chemotherapy response in metastatic colorectal cancer: a single institutional study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016634/
https://www.ncbi.nlm.nih.gov/pubmed/31952366
http://dx.doi.org/10.3390/cells9010219
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