Prognostic and predictive impact of consensus molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study

Abstract

Introduction: The consensus molecular subtypes (CMS) demonstrated prognostic value in metastatic colorectal cancer (mCRC). Similarly, a prognostic impact was suggested for the pre-consensus CRCAssigner (CRCA) classifier in early stages. The potential predictive role of these classifiers with regard to the choice of the first-line therapy has not been established. We investigated the prognostic and predictive impact of CMS and CRCA subtypes among mCRC patients treated in the TRIBE2 study. Methods: Among 679 randomized patients, 426 and 428 (63%) samples were profiled according to CMS and CRCA classifications, respectively. The prognostic and predictive impact of both CMS and CRCA subtypes was investigated with univariate and multivariate analyses for progression-free survival (PFS), PFS 2 (PFS2), and overall survival (OS). Results: Significant associations of CMS and CRCA subtypes with PFS, PFS2, and OS were demonstrated; the CMS classifier confirmed its independent prognostic value in the multivariable model (P value for PFS/PFS2/OS ¼ 0.01/ 0.07/0.08). The effect of treatment intensification was independent of CMS subtypes (P value for interaction for PFS/PFS2/OS ¼ 0.88/0.75/0.55). A significant interaction effect between CRCA subtypes and treatment arm was demonstrated in PFS (P ¼ 0.02), PFS2 (P ¼ 0.01), and OS (P ¼ 0.008). The benefit of FOLFOXIRI seemed more relevant in the stem-like (PFS, hazard ratio ¼ 0.60; P ¼ 0.03) and mixed subtypes (hazard ratio ¼ 0.44; P ¼ 0.002). These findings were confirmed in a subgroup of patients of the previous TRIBE study. Conclusions: We confirmed the independent prognostic role of CMS classification in mCRC independently of RAS/BRAF status. CRCA classification may help identifying subgroups of patients who may derive more benefit from FOLFOXIRI/ bevacizumab.

The Therapeutic Potential of Tackling Tumor-Induced Dendritic Cell Dysfunction in Colorectal Cancer

“…Besides MSS/MSI stratification, a more comprehensive classification system for CRC has been developed. The Consensus Molecular Subtype system, which divides CRC patients in 4 subtypes based on transcriptome analysis of the tumor and associated stromal and immune cells (38,39). This stratification system suggests that characterizing gene expression of not only tumor cells but also of surrounding tumor-associated cells (such as fibroblasts, leukocytes and endothelial cells) allows better stratification of patients and confers higher predictive value for prognosis, management, and selection of appropriate treatment (40).…”

Identification of a novel lipid metabolism-related gene signature for predicting colorectal cancer survival

“…Consensus molecular subtypes were clustering algorithms with resampling and network-based approaches ( Wilkerson and Hayes, 2010 ). Consensus molecular subtypes revealed prognostic value in metastatic colorectal cancer ( Borelli et al, 2021 ). Here, the consensus molecular subtypes were established using “ConsensusClusterPlus” package in R software ( Wilkerson and Hayes, 2010 ).…”

The Expression Pattern of Hypoxia-Related Genes Predicts the Prognosis and Mediates Drug Resistance in Colorectal Cancer

“…Several commercial platforms, such as CRCassigner and ColoGuidePro, have been utilized in clinic for predicting patients' prognosis and response to chemotherapy. Based on multiple and large cohorts, HGS shows its superiority in broad application and quantitative evaluation against the commercial platforms (Sveen et al, 2012;Borelli et al, 2021). Nevertheless, follow-up clinical trials need to be carried out to further verify the effectiveness of HGS.…”