Cargando…

CMScaller: an R package for consensus molecular subtyping of colorectal cancer pre-clinical models

Colorectal cancers (CRCs) can be divided into four gene expression-based biologically distinct consensus molecular subtypes (CMS). This classification provides a potential framework for stratified treatment, but to identify novel CMS-drug associations, translation of the subtypes to pre-clinical mod...

Descripción completa

Detalles Bibliográficos
Autores principales: Eide, Peter W., Bruun, Jarle, Lothe, Ragnhild A., Sveen, Anita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709354/
https://www.ncbi.nlm.nih.gov/pubmed/29192179
http://dx.doi.org/10.1038/s41598-017-16747-x
_version_ 1783282757090148352
author Eide, Peter W.
Bruun, Jarle
Lothe, Ragnhild A.
Sveen, Anita
author_facet Eide, Peter W.
Bruun, Jarle
Lothe, Ragnhild A.
Sveen, Anita
author_sort Eide, Peter W.
collection PubMed
description Colorectal cancers (CRCs) can be divided into four gene expression-based biologically distinct consensus molecular subtypes (CMS). This classification provides a potential framework for stratified treatment, but to identify novel CMS-drug associations, translation of the subtypes to pre-clinical models is essential. The currently available classifier is dependent on gene expression signals from the immune and stromal compartments of tumors and fails to identify the poor-prognostic CMS4-mesenchymal group in immortalized cell lines, patient-derived organoids and xenografts. To address this, we present a novel CMS classifier based on a filtered set of cancer cell-intrinsic, subtype-enriched gene expression markers. This new classifier, referred to as CMScaller, recapitulated the subtypes in both in vitro and in vivo models (551 in total). Importantly, by analyzing public drug response data from patient-derived xenografts and cell lines, we show that the subtypes are predictive of response to standard CRC drugs. CMScaller is available as an R package.
format Online
Article
Text
id pubmed-5709354
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-57093542017-12-06 CMScaller: an R package for consensus molecular subtyping of colorectal cancer pre-clinical models Eide, Peter W. Bruun, Jarle Lothe, Ragnhild A. Sveen, Anita Sci Rep Article Colorectal cancers (CRCs) can be divided into four gene expression-based biologically distinct consensus molecular subtypes (CMS). This classification provides a potential framework for stratified treatment, but to identify novel CMS-drug associations, translation of the subtypes to pre-clinical models is essential. The currently available classifier is dependent on gene expression signals from the immune and stromal compartments of tumors and fails to identify the poor-prognostic CMS4-mesenchymal group in immortalized cell lines, patient-derived organoids and xenografts. To address this, we present a novel CMS classifier based on a filtered set of cancer cell-intrinsic, subtype-enriched gene expression markers. This new classifier, referred to as CMScaller, recapitulated the subtypes in both in vitro and in vivo models (551 in total). Importantly, by analyzing public drug response data from patient-derived xenografts and cell lines, we show that the subtypes are predictive of response to standard CRC drugs. CMScaller is available as an R package. Nature Publishing Group UK 2017-11-30 /pmc/articles/PMC5709354/ /pubmed/29192179 http://dx.doi.org/10.1038/s41598-017-16747-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Eide, Peter W.
Bruun, Jarle
Lothe, Ragnhild A.
Sveen, Anita
CMScaller: an R package for consensus molecular subtyping of colorectal cancer pre-clinical models
title CMScaller: an R package for consensus molecular subtyping of colorectal cancer pre-clinical models
title_full CMScaller: an R package for consensus molecular subtyping of colorectal cancer pre-clinical models
title_fullStr CMScaller: an R package for consensus molecular subtyping of colorectal cancer pre-clinical models
title_full_unstemmed CMScaller: an R package for consensus molecular subtyping of colorectal cancer pre-clinical models
title_short CMScaller: an R package for consensus molecular subtyping of colorectal cancer pre-clinical models
title_sort cmscaller: an r package for consensus molecular subtyping of colorectal cancer pre-clinical models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709354/
https://www.ncbi.nlm.nih.gov/pubmed/29192179
http://dx.doi.org/10.1038/s41598-017-16747-x
work_keys_str_mv AT eidepeterw cmscalleranrpackageforconsensusmolecularsubtypingofcolorectalcancerpreclinicalmodels
AT bruunjarle cmscalleranrpackageforconsensusmolecularsubtypingofcolorectalcancerpreclinicalmodels
AT lotheragnhilda cmscalleranrpackageforconsensusmolecularsubtypingofcolorectalcancerpreclinicalmodels
AT sveenanita cmscalleranrpackageforconsensusmolecularsubtypingofcolorectalcancerpreclinicalmodels