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.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.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.doi http://dx.doi.org/10.1371/journal.pone.0203051
  • dc.identifier.issn 1932-6203
  • dc.identifier.uri http://hdl.handle.net/10230/41960
  • 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.accessRights info:eu-repo/semantics/openAccess
  • 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.type.version info:eu-repo/semantics/publishedVersion

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