ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Intratumor CMS Heterogeneity Impacts Patient Prognosis in Localized Colon Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- CT-based radiogenomic analysis to predict high-risk colon cancer (ATTRACT): a multicentric trial.European radiology · 2025Trial
- SLC39-driven zinc influx orchestrates pleiotropic tumor-immune system cross-talk to establish immune suppression in colorectal cancer.Science advances · 2026Article
- TP53 mutation is associated with improved disease control in patients with advanced RAS wild-type colorectal adenocarcinoma treated with cetuximab and pembrolizumab.International journal of cancer · 2026Article
- Combination immunotherapy for colorectal cancer: Clinical applications, rationale, challenges, and future perspectives.Cell reports. Medicine · 2026Review
- Potentiation of a Porous Silicon Therapeutic Vaccine in Colorectal Cancer via Oxaliplatin-Mediated Regulation of Myeloid-Driven Immunosuppression.Journal of functional biomaterials · 2026Article
- Exploratory biomarker analysis of RAS/BRAF somatic mutations and gene expression signatures for predicting treatment effects of aflibercept in the velour trial.NPJ precision oncology · 2026Article
- Novel nested conformal prediction analysis to unravel complexity in patient subtyping.Frontiers in artificial intelligence · 2026Article
- Colorectal cancer organoids drive hypoxia, TGF-β, and patient-specific diversification of NK cell activation programs.Journal for immunotherapy of cancer · 2025Article
- Regulatory Mechanisms of Lipid Rafts in Remodeling the Tumor Immune Microenvironment of Colorectal Cancer and Targeted Therapeutic Strategies.Biomolecules · 2025Review
- Consensus Molecular Subtypes (CMS) Classification: a progress towards Subtype-Driven treatments in colorectal cancer.World journal of surgical oncology · 2025Review
- Advances in Hereditary Colorectal Cancer: How Precision Medicine Is Changing the Game.Cancers · 2025Review
- Plasticity and Functional Heterogeneity of Cancer-Associated Fibroblasts.Cancer research · 2025Review
- Multi-modal clustering reveals event-free patient subgroup in colorectal cancer survival.NPJ systems biology and applications · 2025Article
- Entering the Era of Multidimensional Prognostication for Personalized Risk Assessment in Stage III Colon Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- Prognostic Models From Transcriptomic Signatures of the Tumor Microenvironment and Cell Cycle in Stage III Colon Cancer From PETACC-8 and IDEA-France Trials.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- Does side matter? Deciphering mechanisms that underpin side-dependent pathogenesis and therapy response in colorectal cancer.Molecular cancer · 2025Review
- NanoCMSer: a consensus molecular subtype stratification tool for fresh-frozen and paraffin-embedded colorectal cancer samples.Molecular oncology · 2025Article
- Reproducible processing of TCGA regulatory networks.GigaScience · 2025Article
- Targeting stemness pathways modulates macrophage polarization and reprograms the tumor microenvironment.Frontiers in immunology · 2025Article
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Abstract
purposeThe consensus molecular subtypes (CMS) represent a significant advance in the understanding of intertumor heterogeneity in colon cancer. Intratumor heterogeneity (ITH) is the new frontier for refining prognostication and understanding treatment resistance. This study aims at deciphering the transcriptomic ITH of colon cancer and understanding its potential prognostic implications. EXPERIMENTAL
designWe deconvoluted the transcriptomic profiles of 1,779 tumors from the PETACC8 trial and 155 colon cancer cell lines as weighted sums of the four CMSs, using the Weighted In Silico Pathology (WISP) algorithm. We assigned to each tumor and cell line a combination of up to three CMS subtypes with a threshold above 20%.
resultsOver 55% of tumors corresponded to mixtures of at least two CMSs, demonstrating pervasive ITH in colon cancer. Of note, ITH was associated with shorter disease-free survival (DFS) and overall survival, [HR, 1.34; 95% confidence interval (CI; 1.12-1.59), 1.40, 95% CI (1.14-1.71), respectively]. Moreover, we uncovered specific combinations of CMS associated with dismal prognosis. In multivariate analysis, ITH represents the third parameter explaining DFS variance, after T and N stages. At a cellular level, combined WISP and single-cell transcriptomic analysis revealed that most colon cancer cell lines are a mixture of cells falling into different CMSs, indicating that ITH may correspond to distinct functional statuses of colon cancer cells.
conclusionsThis study shows that CMS-based transcriptomic ITH is frequent in colon cancer and impacts its prognosis. CMS-based transcriptomic ITH may correspond to distinct functional statuses of colon cancer cells, suggesting plasticity between CMS-related cell populations. Transcriptomic ITH deserves further assessment in the context of personalized medicine.
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