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Open AccessArticle

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

1
Translational Oncology Division, OncoHealth Institute, Fundacion Jimenez Diaz University Hospital, Av. Reyes Católicos 2, 28040 Madrid, Spain
2
Oncology Department, OncoHealth Institute, Fundacion Jimenez Diaz University Hospital, Av. Reyes Católicos 2, 28040 Madrid, Spain
3
Pathology Department, Fundacion Jimenez Diaz University Hospital, Av. Reyes Católicos 2, 28040 Madrid, Spain
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START Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz, Av. de los Reyes Católicos, 2, 28040 Madrid, Spain
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START Madrid-Hospital HM Sanchinarro, Calle de Oña, 10, 28050 Madrid, Spain
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Oncology Department, University Hospital Infanta Leonor, Avenida de la Gran Vía del Este, 80, 28031 Madrid; Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(1), 219; https://doi.org/10.3390/cells9010219 (registering DOI)
Received: 12 December 2019 / Revised: 7 January 2020 / Accepted: 11 January 2020 / Published: 15 January 2020
(This article belongs to the Special Issue Role of KRAS Mutations in Colorectal Cancer)
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. View Full-Text
Keywords: KRAS; BRAF; metastatic colorectal cancer; prognosis; chemotherapy; anti-EGFR; biomarker KRAS; BRAF; metastatic colorectal cancer; prognosis; chemotherapy; anti-EGFR; biomarker
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Garcia-Carbonero, N.; Martinez-Useros, J.; Li, W.; Orta, A.; Perez, N.; Carames, C.; Hernandez, T.; Moreno, I.; Serrano, G.; Garcia-Foncillas, J. KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study. Cells 2020, 9, 219.

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