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Colorectal cancer molecular classification using BRAF, KRAS, microsatellite instability and CIMP status: prognostic implications and response to chemotherapy

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dc.contributor.author Murcia, Oscar
dc.contributor.author Juárez, Míriam
dc.contributor.author Rodríguez-Soler, María
dc.contributor.author Hernández-Illán, Eva
dc.contributor.author Giner-Calabuig, Mar
dc.contributor.author Alustiza, Miren
dc.contributor.author Egoavil, Cecilia
dc.contributor.author Castillejo, Adela
dc.contributor.author Alenda, Cristina
dc.contributor.author Barbera, Victor Manuel
dc.contributor.author Mangas-Sanjuan, Carolina
dc.contributor.author Yuste, Ana
dc.contributor.author Bujanda, Luis
dc.contributor.author Clofent, Juan
dc.contributor.author Andreu García, Montserrat
dc.contributor.author Castells, Antoni
dc.contributor.author Llor, Xavier
dc.contributor.author Zapater, Pedro
dc.contributor.author Jover, Rodrigo
dc.date.accessioned 2019-07-09T07:28:23Z
dc.date.available 2019-07-09T07:28:23Z
dc.date.issued 2018
dc.identifier.citation Murcia O, Juárez M, Rodríguez-Soler M, Hernández-Illán E, Giner-Calabuig M, Alustiza M. et al. Colorectal cancer molecular classification using BRAF, KRAS, microsatellite instability and CIMP status: prognostic implications and response to chemotherapy. PLoS One. 2018 Sep 6;13(9):e0203051. DOI: 10.1371/journal.pone.0203051
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10230/41960
dc.description.abstract OBJECTIVE: The aim of this study was to validate a molecular classification of colorectal cancer (CRC) based on microsatellite instability (MSI), CpG island methylator phenotype (CIMP) status, BRAF, and KRAS and investigate each subtype's response to chemotherapy. DESIGN: This retrospective observational study included a population-based cohort of 878 CRC patients. We classified tumours into five different subtypes based on BRAF and KRAS mutation, CIMP status, and MSI. Patients with advanced stage II (T4N0M0) and stage III tumours received 5-fluoruracil (5-FU)-based chemotherapy or no adjuvant treatment based on clinical criteria. The main outcome was disease-free survival (DFS). RESULTS: Patients with the combination of microsatellite stable (MSS) tumours, BRAF mutation and CIMP positive exhibited the worst prognosis in univariate (log rank P<0.0001) and multivariate analyses (hazard ratio 1.75, 95% CI 1.05-2.93, P = 0.03) after adjusting for age, sex, chemotherapy, and TNM stage. Treatment with 5-FU-based regimens improved prognosis in patients with the combination of MSS tumours, KRAS mutation and CIMP negative (log rank P = 0.003) as well as in patients with MSS tumours plus BRAF and KRAS wild-type and CIMP negative (log-rank P<0.001). After adjusting for age, sex, and TNM stage in the multivariate analysis, only patients with the latter molecular combination had independently improved prognosis after adjuvant chemotherapy (hazard ratio 2.06, 95% CI 1.24-3.44, P = 0.005). CONCLUSION: We confirmed the prognostic value of stratifying CRC according to molecular subtypes using MSI, CIMP status, and somatic KRAS and BRAF mutation. Patients with traditional chromosomally unstable tumours obtained the best benefit from adjuvant 5-FU-based chemotherapy.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Public Library of Science (PLoS)
dc.rights Copyright © 2018 Murcia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Còlon -- Càncer -- Aspectes genètics
dc.subject.other Colon -- Càncer -- Quimioteràpia
dc.title Colorectal cancer molecular classification using BRAF, KRAS, microsatellite instability and CIMP status: prognostic implications and response to chemotherapy
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0203051
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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