e14544: Connecting gene expression subtypes of colorectal cancer (CRC) with cell lines and drug resistance

Détails

ID Serval
serval:BIB_9300DECC71BC
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Institution
Titre
e14544: Connecting gene expression subtypes of colorectal cancer (CRC) with cell lines and drug resistance
Titre de la conférence
Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
Auteur⸱e⸱s
Budinska E., Wilding J., Popovici VC, Missiaglia E., Roth A., Bosman F., Delorenzi M., Bodmer W., Tejpar S.
Adresse
Chicago, USA, May 31 - June 04, 2013
ISBN
0732-183X
ISSN-L
0732-183X
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
31
Série
Journal of Clinical Oncology
Pages
e14544
Langue
anglais
Résumé
Background: We identified CRC gene expression subtypes (ASCO 2012, #3511), which associate with established parameters of outcome as well as relevant biological motifs. We now substantiate their biological and potentially clinical significance by linking them with cell line data and drug sensitivity, primarily attempting to identify models for the poor prognosis subtypes Mesenchymal and CIMP-H like (characterized by EMT/stroma and immune-associated gene modules, respectively). Methods: We analyzed gene expression profiles of 35 publicly available cell lines with sensitivity data for 82 drug compounds, and our 94 cell lines with data on sensitivity for 7 compounds and colony morphology. As in vitro, stromal and immune-associated genes loose their relevance, we trained a new classifier based on genes expressed in both systems, which identifies the subtypes in both tissue and cell cultures. Cell line subtypes were validated by comparing their enrichment for molecular markers with that of our CRC subtypes. Drug sensitivity was assessed by linking original subtypes with 92 drug response signatures (MsigDB) via gene set enrichment analysis, and by screening drug sensitivity of cell line panels against our subtypes (Kruskal-Wallis test). Results: Of the cell lines 70% could be assigned to a subtype with a probability as high as 0.95. The cell line subtypes were significantly associated with their KRAS, BRAF and MSI status and corresponded to our CRC subtypes. Interestingly, the cell lines which in matrigel created a network of undifferentiated cells were assigned to the Mesenchymal subtype. Drug response studies revealed potential sensitivity of subtypes to multiple compounds, in addition to what could be predicted based on their mutational profile (e.g. sensitivity of the CIMP-H subtype to Dasatinib, p<0.01). Conclusions: Our data support the biological and potentially clinical significance of the CRC subtypes in their association with cell line models, including results of drug sensitivity analysis. Our subtypes might not only have prognostic value but might also be predictive for response to drugs. Subtyping cell lines further substantiates their significance as relevant model for functional studies.
Web of science
Création de la notice
10/08/2016 8:53
Dernière modification de la notice
20/08/2019 14:55
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