Context matters-consensus molecular subtypes of colorectal cancer as biomarkers for clinical trials

Annals of Oncology : Official Journal of the European Society for Medical Oncology
E FontanaAnguraj Sadanandam

Abstract

The Colorectal Cancer Subtyping Consortium identified four gene expression consensus molecular subtypes, CMS1 (immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal), using multiple microarray or RNA-sequencing datasets of primary tumor samples mainly from early stage colon cancer patients. Consequently, rectal tumors and stage IV tumors (possibly reflective of more aggressive disease) were underrepresented, and no chemo- and/or radiotherapy pretreated samples or metastatic lesions were included. In view of their possible effect on gene expression and consequently subtype classification, sample source and treatments received by the patients before collection must be carefully considered when applying the classifier to new datasets. Recently, several correlative analyses of clinical trials demonstrated the applicability of this classification to the metastatic setting, confirmed the prognostic value of CMS subtypes after relapse and hinted at differential sensitivity to treatments. Here, we discuss why contexts and equivocal factors need to be taken into account when analyzing clinical trial data, including potential selection biases, type of platform, and type of algorithm used for subtype prediction. This perspect...Continue Reading

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Citations

Jul 11, 2019·Nature Reviews. Clinical Oncology·Anita SveenRagnhild A Lothe
Dec 24, 2019·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A SveenR Dienstmann
Mar 29, 2020·Signal Transduction and Targeted Therapy·Yuan-Hong XieJing-Yuan Fang
Jul 30, 2020·Annals of Gastroenterological Surgery·Ho Seung Kim, Nam Kyu Kim
Oct 3, 2020·Annals of Gastroenterological Surgery·Hiroshi SawayamaHideo Baba
Oct 29, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jeffrey S MorrisDipen M Maru
Jan 17, 2021·Oncogene·P N Plowman, C E Plowman
Jan 11, 2021·Current Opinion in Genetics & Development·Tamsin Rm LannaganOwen J Sansom
Feb 13, 2021·International Journal of Molecular Sciences·Stanislaw SupplittIzabela Laczmanska
Nov 1, 2020·Cancers·Sophie Mouillet-Richard, Pierre Laurent-Puig

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Methods Mentioned

BETA
Subtyping
biopsies

Software Mentioned

nCounter
R ‘ CMSclassifier
CRCAssigner
CMScaller
CRCSC

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