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Sci Rep. 2017 Nov 30;7(1):16618. doi: 10.1038/s41598-017-16747-x.

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

Eide PW1,2,3, Bruun J1,2, Lothe RA1,2,3, Sveen A4,5.

Author information

1
Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, NO-0424, Norway.
2
K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, NO-0424, Norway.
3
Institute for Clinical Medicine, University of Oslo, Oslo, NO-0318, Norway.
4
Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, NO-0424, Norway. anita.sveen@rr-research.no.
5
K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, NO-0424, Norway. anita.sveen@rr-research.no.

Abstract

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.

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