Abstract 338P
Background
In the last years, a great effort has been made to unify different independent colorectal cancer (CRC) molecular classification systems into four consensus molecular subtypes (CMS). The four subtypes are found to be associated with distinct microenvironmental features and clinical outcome, although metabolic singularities are not well established. Metabolic dysregulation has been reported as a hallmark of CMS3 but metabolic heterogeneity among other subtypes has not been investigated. Here, taking into account the increasing evidence on the importance, for determining response to therapies, of the metabolic crosstalk between cancer cells, tumor microenvironment and immune cells, we investigated the metabolic singularities in the four CMS using a genetic immune-metabolic signature (IMMETCOLS).
Methods
We evaluated the correlation of CMS signature using CMS classifier with single sample predictor (SSP) and the new IMMETCOLS signature (10-gene expression classifier) that separates three clusters; IMC1: Mesenchymal high glycolytic/low Oxphos, IMC2: Epithelial low glycolytic/high Oxphos and IMC3: Epithelial high glycolytic/high Oxphos, in two public data sets (TCGA, n=512 patients and GES, n=1328 patients). CMS and IMMETCOLS interactions with overall survival were also analyzed.
Results
IMMETCOLS clusters (ICM1-33%, ICM2-14%, IMC3-53%) and CMS subtypes (CMS1-24%, CMS2-44%, CMS3-14%, CMS4-18%) are distributed as previously published. CMS1 is characterized by a mixture of IMC1 (47%) and IMC3 (47%) and CMS4 is basically constituted by IMC1 (90%). Finally, CMS2 and CMS3 subtypes are mainly distributed in IMC3 (71%) and IMC2 clusters (22%). Either CMS4 and IMC1 confers poor prognostic. Importantly, our data demonstrated that ICM2 has the worst overall survival in the CMS2 subtype.
Conclusions
IMMETCOLS signature refines CMS prognosis in CRC patients and potentially allows specific metabolic interventions in CMS subtypes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J. Maurel: Financial Interests, Personal, Advisory Role: Sirtex Medical; Financial Interests, Personal, Advisory Board: Pierre Fabre, Shire, AstraZeneca, Servier; Financial Interests, Personal, Other, Research Funding: Merck Serono, Amgen, NanoString Technologies, Biocartis, Roche, Incyte. All other authors have declared no conflicts of interest.