ArticleBMC cancer2019
External validation of molecular subtype classifications of colorectal cancer based on microsatellite instability, CIMP, BRAF and KRAS.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Large-scale external validation and meta-analysis of gene methylation biomarkers in tumor tissue for colorectal cancer prognosis.EBioMedicine · 2024Pooled it
- Genomic characterization of colorectal tumors: insights into significantly mutated genes, pathways, and survival outcomes.BMC cancer · 2025Article
- Is ypTNM staging a comparable predictor as pTNM staging for survival in non-metastatic rectal cancer after preoperative chemoradiation therapy?Oncology research · 2024Article
- Transcriptomes of the tumor-adjacent normal tissues are more informative than tumors in predicting recurrence in colorectal cancer patients.Journal of translational medicine · 2023Article
- Validation of the prognostic value of CD3 and CD8 cell densities analogous to the Immunoscore® by stage and location of colorectal cancer: an independent patient cohort study.The journal of pathology. Clinical research · 2023Article
- Swarm learning for decentralized artificial intelligence in cancer histopathology.Nature medicine · 2022Article
- Novel molecular classification of colorectal cancer and correlation with survival.Saudi journal of biological sciences · 2022Article
- Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes.JNCI cancer spectrum · 2021Article
- Effects of Somatic Methylation in Colonic Polyps on Risk of Developing Metachronous Advanced Colorectal Lesions.Cancers · 2021Article
- Contribution of Epithelial and Gut Microbiome Inflammatory Biomarkers to the Improvement of Colorectal Cancer Patients' Stratification.Frontiers in oncology · 2021Review
- Effective management of advanced colon cancer genotyping microsatellite stable/microsatellite instable-low with Kirsten rat sarcoma viral oncogene mutation using nivolumab plus ipilimumab combined with regorafenib and irinotecan: A case report.SAGE open medical case reports · 2021Article
- Response to neoadjuvant treatment among rectal cancer patients in a population-based cohort.International journal of colorectal disease · 2021Article
- Genomic Alterations and Their Implications on Survival in Nonmetastatic Colorectal Cancer: Status Quo and Future Perspectives.Cancers · 2020Review
- Prognostic and Predictive Molecular Biomarkers for Colorectal Cancer: Updates and Challenges.Cancers · 2020Review
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13 authors.
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Abstract
backgroundCompeting molecular classification systems have been proposed to complement the TNM staging system for a better prediction of survival in colorectal cancer (CRC). However, validation studies are so far lacking. The aim of this study was to validate and extend previously published molecular classifications of CRC in a large independent cohort of CRC patients.
methodsCRC patients were recruited into a population-based cohort study (DACHS). Molecular subtypes were categorized based on three previously published classifications. Cox-proportional hazard models, based on the same set of patients and using the same confounders as reported by the original studies, were used to determine overall, cancer-specific, or relapse-free survival for each subtype. Hazard ratios and confidence intervals, as well as Kaplan-Meier plots were compared to those reported by the original studies.
resultsWe observed similar patterns of worse survival for the microsatellite stable (MSS)/BRAF-mutated and MSS/KRAS-mutated subtypes in our validation analyses, which were included in two of the validated classifications. Of the two MSI subtypes, one defined by additional presence of CIMP-high and BRAF-mutation and the other by tumors negative for CIMP, BRAF and KRAS-mutations, we could not confirm associations with better prognosis as suggested by one of the classifications. For two of the published classifications, we were able to provide results for additional subgroups not included in the original studies (men, other disease stages, other locations).
conclusionsExternal validation of three previously proposed classifications confirmed findings of worse survival for CRC patients with MSS subtypes and BRAF or KRAS mutations. Regarding MSI subtypes, other patient characteristics such as stage of the tumor, may influence the potential survival benefit. Further integration of methylation, genetic, and immunological information is needed to develop and validate a comprehensive classification that will have relevance for use in clinical practice.
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