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

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.

Long noncoding RNA MIR31HG is a bona fide prognostic marker with colorectal cancer cell‐intrinsic properties

“…S17a and b). However, by Camera gene set analysis of 70 preselected CMS and CRC informative gene sets (Fig. c ), MIR31 outlier cell lines were found to show strong enrichment for epithelial‐mesenchymal transition (EMT) and immune‐related gene sets such as TGF‐β, TNF‐α/NFκB and IFN‐α/γ, as well as downregulation of MYC and HNF4A target genes (false discovery rate (FDR) adjusted p < 0.005).…”

“…pCRCs in the Oslo series were classified using the classifyCMS.RF function in the R package CMSclassifier with default posterior probability threshold . CRC cell lines were classified according to CMS using CMScaller . Cell line differentiation state was determined as previously described …”

“…. Classification of pCRCs according to the CRC intrinsic subtypes (CRIS) was performed using CMScaller function in the R package CMScaller with CRIS template genes from Supplementary Table 8 in Ref. .…”

Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments

“…Consensus molecular subtypes (CMS) can be used to divide CRCs into four biologically distinct and clinically relevant subtypes: CMS1 (MSI-like), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal) [63,64]. Recent studies also highlight left-sided (descending colon, sigmoid colon, and rectum) and right-sided (caecum, ascending colon, and transverse colon) colon cancers as having distinct molecular features which result in different outcomes and drug responses [65].…”

Bi-clustering based biological and clinical characterization of colorectal cancer in complementary to CMS classification

“…We applied the R package CMSclassifier to predict the CMS classification of each sample in the eight data sets (39), by which each sample will be predicted with four CMS scores representing its similarity to the four CMS classes. One sample is classified to one subtype if its CMS score of the subtype is larger than 0.5 and a sample is considered as with multiple-classification if both top two CMS scores are larger than 0.5 and the difference between the two scores is smaller than 0.1.…”