Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer
Open accessAbstract
Gene expression-based subtypes of colorectal cancer have clinical relevance, but the representativeness of primary tumors and the consensus molecular subtypes (CMS) for metastatic cancers is not well known. We investigated the metastatic heterogeneity of CMS. The best approach to subtype translation was delineated by comparisons of transcriptomic profiles from 317 primary tumors and 295 liver metastases, including multi-metastatic samples from 45 patients and 14 primary-metastasis sets. Associations were validated in an external data set (n = 618). Projection of metastases onto principal components of primary tumors showed that metastases were depleted of CMS1-immune/CMS3-metabolic signals, enriched for CMS4-mesenchymal/stromal signals, and heavily influenced by the microenvironment. The tailored CMS classifier (available in an updated version of the R package CMScaller) therefore implemented an approach to regress out the liver tissue background. The majority of classified metastases were either CMS2 or CMS4. Nonetheless, subtype switching and inter-metastatic CMS heterogeneity were frequent and increased with sampling intensity. Poor-prognostic value of CMS1/3 metastases was consistent in the context of intra-patient tumor heterogeneity.
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The tumour stroma represents an attractive therapeutic target in metastatic colorectal cancer to revert immunosuppression and immune exclusion in both primary and metastatic colorectal cancer.
“suggesting that the tumour stroma represents an attractive therapeutic target in mCRC to revert immunosuppression and immune exclusion not only in primary but also in metastatic CRC.”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [123]
In colorectal liver metastases, transcriptomic classification using a modified CMS classifier resulted in enrichment of CMS2 and CMS4 subtypes compared with primary tumours.
“In colorectal liver metastases, transcriptomic classification using a modified CMS classifier resulted in an enrichment of the CMS2 and CMS4 subtypes compared with primary tumours,123”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [123]
The CMS4 profile may come up upon metastasis in various tissues.
“The CMS4 profile may also come up upon metastasis in various tissues (10, 22, 23)”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [10]
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References 47 · Cited by 70
- Authors
- Eide, P. W., Moosavi, S. H., Eilertsen, I. A., Brunsell, T. H., Langerud, J., Berg, K. C. G., Røsok, B. I., Bjørnbeth, B. A., Nesbakken, A., Lothe, R. A., & Sveen, A.
- Affiliations
- Oslo University Hospital (NO)
- Corresponding author
- Sveen, Anita
- ORCID
- Venue
- npj Genomic Medicine
- Published
- 2021-07-14
- Volume
- 6
- Issue
- 1
- Pages
- 59-59
- ISSN
- 2056-7944 (ISSN-L)
- PMC
- PMC8280229
- OpenAlex
- W3182666770
- Cited by
- 70
- References
- 47
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 16 · 2023: 14 · 2022: 12 · 2021: 3
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Genomic Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- Kreftforeningen (182759‐2016, 208336-2019)
- Norges Forskningsråd (250993, 287899)
- Helse Sør-Øst RHF (2016123, 2019042, 2017102)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Keywords
- colorectal cancer, consensus molecular subtypes, metastatic heterogeneity, liver metastasis, subtype switching, tumor microenvironment, metabolic signals, mesenchymal subtype, prognostic value
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