Interconnectivity between molecular subtypes and tumor stage in colorectal cancer
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Abstract
Background: There are profound individual differences in clinical outcomes between colorectal cancers (CRCs) presenting with identical stage of disease. Molecular stratification, in conjunction with the traditional TNM staging, is a promising way to predict patient outcomes. We investigated the interconnectivity between tumor stage and tumor biology reflected by the Consensus Molecular Subtypes (CMSs) in CRC, and explored the possible value of these insights in patients with stage II colon cancer. Methods: We performed a retrospective analysis using clinical records and gene expression profiling in a meta-cohort of 1040 CRC patients. The interconnectivity of tumor biology and disease stage was assessed by investigating the association between CMSs and TNM classification. In order to validate the clinical applicability of our findings we employed a meta-cohort of 197 stage II colon cancers. Results: CMS4 was significantly more prevalent in advanced stages of disease (stage I 9.8% versus stage IV 38.5%, p < 0.001). The observed differential gene expression between cancer stages is at least partly explained by the biological differences as reflected by CMS subtypes. Gene signatures for stage III-IV and CMS4 were highly correlated (r = 0.77, p < 0.001). CMS4 cancers showed an increased progression rate to more advanced stages (CMS4 compared to CMS2: 1.25, 95% CI: 1.08–1.46). Patients with a CMS4 cancer had worse survival in the high-risk stage II tumors compared to the total stage II cohort (5-year DFS 41.7% versus 100.0%, p = 0.008). Conclusions: Considerable interconnectivity between tumor biology and tumor stage in CRC exists. This implies that the TNM stage, in addition to the stage of progression, might also reflect distinct biological disease entities. These insights can potentially be utilized to optimize identification of high-risk stage II colon cancers.
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The proportion of CMS4 cases increases with disease stage, ranging from 10% in stage 1 to 38.5% in stage 4 patients.
“the proportion of CMS4 cases was shown to gradually increase with stage, ranging from 10% in stage 1 to 38.5% in stage 4 patients (16).”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [16]
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- Authors
- Coebergh van den Braak, R. R. J., ten Hoorn, S., Sieuwerts, A. M., Tuynman, J. B., Smid, M., Wilting, S. M., Martens, J. W. M., Punt, C. J. A., Foekens, J. A., Medema, J. P., IJzermans, J. N. M., & Vermeulen, L.
- Affiliations
- Erasmus MC (NL)
- Amsterdam University Medical Centers (NL)
- University Medical Center Utrecht (NL)
- Corresponding author
- Vermeulen, L.
- ORCID
- Venue
- BMC Cancer
- Published
- 2020-09-04
- Volume
- 20
- Issue
- 1
- Pages
- 850-850
- ISSN
- 1471-2407 (ISSN-L)
- PMC
- PMC7473811
- OpenAlex
- W3083088281
- Cited by
- 27
- References
- 25
- Citations by year
- 2026: 4 · 2024: 7 · 2022: 2 · 2021: 13 · 2020: 1
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Cancer (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Pure Amsterdam UMC (acceptedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- New York Stem Cell Foundation (NYSCF-I-R43)
- KWF Kankerbestrijding ((UVA2014-7245 and UVA2013-6331)
- Worldwide Cancer Research (14-1164)
- Maag Lever Darm Stichting (MLDS-CDG 14-03)
- H2020 European Research Council (ERG-StG 638193)
- ZonMw (Vidi 016.156.308)
- Fonds NutsOhra (0903-011)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- colorectal cancer, consensus molecular subtypes, tumor stage, TNM staging, stage II colon cancer, CMS4, disease progression, gene expression signatures, molecular stratification, disease-free survival
- MeSH terms
- Aged, Colonic Neoplasms, Female, Humans, Male, Middle Aged, Neoplasm Staging, Prognosis, Retrospective Studies, Risk, Gene Expression Regulation, Neoplastic, Disease-Free Survival, Gene Expression Profiling, Kaplan-Meier Estimate, Microsatellite Instability, Transcriptome
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