title: External validation of molecular subtype classifications of colorectal cancer based on microsatellite instability, CIMP, BRAF and KRAS
creator: Alwers, Elizabeth
creator: Bläker, Hendrik
creator: Walter, Viola
creator: Jansen, Lina
creator: Kloor, Matthias
creator: Arnold, Alexander
creator: Sieber-Frank, Julia
creator: Herpel, Esther
creator: Tagscherer, Katrin E.
creator: Roth, Wilfried
creator: Chang-Claude, Jenny
creator: Brenner, Hermann
creator: Hoffmeister, Michael
subject: ddc-610
subject: 610 Medical sciences Medicine
description: Background: Competing molecular classification systems have been proposed to complement the TNM staging system for a better prediction of survival in colorectal cancer (CRC). However, validation studies are so far lacking. The aim of this study was to validate and extend previously published molecular classifications of CRC in a large independent cohort of CRC patients.       Methods: CRC patients were recruited into a population-based cohort study (DACHS). Molecular subtypes were categorized based on three previously published classifications. Cox-proportional hazard models, based on the same set of patients and using the same confounders as reported by the original studies, were used to determine overall, cancer-specific, or relapse-free survival for each subtype. Hazard ratios and confidence intervals, as well as Kaplan-Meier plots were compared to those reported by the original studies.       Results: We observed similar patterns of worse survival for the microsatellite stable (MSS)/BRAF-mutated and MSS/KRAS-mutated subtypes in our validation analyses, which were included in two of the validated classifications. Of the two MSI subtypes, one defined by additional presence of CIMP-high and BRAF-mutation and the other by tumors negative for CIMP, BRAF and KRAS-mutations, we could not confirm associations with better prognosis as suggested by one of the classifications. For two of the published classifications, we were able to provide results for additional subgroups not included in the original studies (men, other disease stages, other locations).    Conclusions: External validation of three previously proposed classifications confirmed findings of worse survival for CRC patients with MSS subtypes and BRAF or KRAS mutations. Regarding MSI subtypes, other patient characteristics such as stage of the tumor, may influence the potential survival benefit. Further integration of methylation, genetic, and immunological information is needed to develop and validate a comprehensive classification that will have relevance for use in clinical practice.
publisher: BioMed Central ; Springer
date: 2019
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/26800/1/12885_2019_Article_5842.pdf
identifier: DOI:
identifier: urn:nbn:de:bsz:16-heidok-268008
identifier:   Alwers, Elizabeth ; Bläker, Hendrik ; Walter, Viola ; Jansen, Lina ; Kloor, Matthias ; Arnold, Alexander ; Sieber-Frank, Julia ; Herpel, Esther ; Tagscherer, Katrin E. ; Roth, Wilfried ; Chang-Claude, Jenny ; Brenner, Hermann ; Hoffmeister, Michael  (2019) External validation of molecular subtype classifications of colorectal cancer based on microsatellite instability, CIMP, BRAF and KRAS.  BMC Cancer, 19 (681).  pp. 1-10.  ISSN 1471-2407     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/26800/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng