Molecular signatures reflecting microenvironmental metabolism and chemotherapy-induced immunogenic cell death in colorectal liver metastases

Oncotarget
Olga ØstrupKjersti Flatmark

Abstract

Metastatic colorectal cancer (CRC) is associated with highly variable clinical outcome and response to therapy. The recently identified consensus molecular subtypes (CMS1-4) have prognostic and therapeutic implications in primary CRC, but whether these subtypes are valid for metastatic disease is unclear. We performed multi-level analyses of resectable CRC liver metastases (CLM) to identify molecular characteristics of metastatic disease and evaluate the clinical relevance. In this ancillary study to the Oslo-CoMet trial, CLM and tumor-adjacent liver tissue from 46 patients were analyzed by profiling mutations (targeted sequencing), genome-wide copy number alteration (CNAs), and gene expression. Somatic mutations and CNAs detected in CLM were similar to reported primary CRC profiles, while CNA profiles of eight metastatic pairs suggested intra-patient divergence. A CMS classifier tool applied to gene expression data, revealed the cohort to be highly enriched for CMS2. Hierarchical clustering of genes with highly variable expression identified two subgroups separated by high or low expression of 55 genes with immune-related and metabolic functions. Importantly, induction of genes and pathways associated with immunogenic cell dea...Continue Reading

Associated Clinical Trials

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Feb 24, 2019·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E FontanaA Sadanandam
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Jul 15, 2021·Future Science OA·Yee Chen LauRachel Purcell

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Methods Mentioned

BETA
biopsies
PCR
chip
AmpliSeq
Feature Extraction

Clinical Trials Mentioned

NCT01516710

Software Mentioned

BioConductor
Ingenuity Pathway Analysis ( IPA )
Linear Models for Microarray Data ( LIMMA )
LIMMA
CoMet
R packages
Feature Extraction
Torrent Suite Variant Caller
Agilent
. plus

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