Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer.

Détails

Ressource 1Télécharger: BIB_DACD8808E86F.P001.pdf (1240.63 [Ko])
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_DACD8808E86F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer.
Périodique
Journal of Pathology
Auteur⸱e⸱s
Budinska E., Popovici V., Tejpar S., D'Ario G., Lapique N., Sikora K.O., Di Narzo A.F., Yan P., Hodgson J.G., Weinrich S., Bosman F., Roth A., Delorenzi M.
ISSN
1096-9896 (Electronic)
ISSN-L
0022-3417
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
231
Numéro
1
Pages
63-76
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defined subgroup. We performed a prior free analysis of CRC heterogeneity on 1113 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed. A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided molecular information beyond that contained in these variables. Morphological features significantly differed between subtypes. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles. Our subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets and, when sufficiently robust, be prospectively assessed for clinical relevance in terms of prognosis and treatment response predictive capacity. Original microarray data were uploaded to the ArrayExpress database (http://www.ebi.ac.uk/arrayexpress/) under Accession Nos E-MTAB-990 and E-MTAB-1026. © 2013 Swiss Institute of Bioinformatics. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/09/2013 9:12
Dernière modification de la notice
20/08/2019 15:59
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