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A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer
Consensus molecular subtypes (CMSs) can guide precision treatment of colorectal cancer (CRC). We aim to identify methylation markers to distinguish between CMS2 and CMS3 in patients with CRC, for which an easy test is currently lacking. To this aim, fresh‐frozen tumor tissue of 239 patients with sta...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637568/ https://www.ncbi.nlm.nih.gov/pubmed/34510716 http://dx.doi.org/10.1002/1878-0261.13098 |
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author | van den Berg, Inge Smid, Marcel Coebergh van den Braak, Robert R. J. van de Wiel, Mark A. van Deurzen, Carolien H. M. de Weerd, Vanja Martens, John W. M. IJzermans, Jan N. M. Wilting, Saskia M. |
author_facet | van den Berg, Inge Smid, Marcel Coebergh van den Braak, Robert R. J. van de Wiel, Mark A. van Deurzen, Carolien H. M. de Weerd, Vanja Martens, John W. M. IJzermans, Jan N. M. Wilting, Saskia M. |
author_sort | van den Berg, Inge |
collection | PubMed |
description | Consensus molecular subtypes (CMSs) can guide precision treatment of colorectal cancer (CRC). We aim to identify methylation markers to distinguish between CMS2 and CMS3 in patients with CRC, for which an easy test is currently lacking. To this aim, fresh‐frozen tumor tissue of 239 patients with stage I‐III CRC was analyzed. Methylation profiles were obtained using the Infinium HumanMethylation450 BeadChip. We performed adaptive group‐regularized logistic ridge regression with post hoc group‐weighted elastic net marker selection to build prediction models for classification of CMS2 and CMS3. The Cancer Genome Atlas (TCGA) data were used for validation. Group regularization of the probes was done based on their location either relative to a CpG island or relative to a gene present in the CMS classifier, resulting in two different prediction models and subsequently different marker panels. For both panels, even when using only five markers, accuracies were > 90% in our cohort and in the TCGA validation set. Our methylation marker panel accurately distinguishes between CMS2 and CMS3. This enables development of a targeted assay to provide a robust and clinically relevant classification tool for CRC patients. |
format | Online Article Text |
id | pubmed-8637568 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86375682021-12-09 A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer van den Berg, Inge Smid, Marcel Coebergh van den Braak, Robert R. J. van de Wiel, Mark A. van Deurzen, Carolien H. M. de Weerd, Vanja Martens, John W. M. IJzermans, Jan N. M. Wilting, Saskia M. Mol Oncol Research Articles Consensus molecular subtypes (CMSs) can guide precision treatment of colorectal cancer (CRC). We aim to identify methylation markers to distinguish between CMS2 and CMS3 in patients with CRC, for which an easy test is currently lacking. To this aim, fresh‐frozen tumor tissue of 239 patients with stage I‐III CRC was analyzed. Methylation profiles were obtained using the Infinium HumanMethylation450 BeadChip. We performed adaptive group‐regularized logistic ridge regression with post hoc group‐weighted elastic net marker selection to build prediction models for classification of CMS2 and CMS3. The Cancer Genome Atlas (TCGA) data were used for validation. Group regularization of the probes was done based on their location either relative to a CpG island or relative to a gene present in the CMS classifier, resulting in two different prediction models and subsequently different marker panels. For both panels, even when using only five markers, accuracies were > 90% in our cohort and in the TCGA validation set. Our methylation marker panel accurately distinguishes between CMS2 and CMS3. This enables development of a targeted assay to provide a robust and clinically relevant classification tool for CRC patients. John Wiley and Sons Inc. 2021-09-30 2021-12 /pmc/articles/PMC8637568/ /pubmed/34510716 http://dx.doi.org/10.1002/1878-0261.13098 Text en © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles van den Berg, Inge Smid, Marcel Coebergh van den Braak, Robert R. J. van de Wiel, Mark A. van Deurzen, Carolien H. M. de Weerd, Vanja Martens, John W. M. IJzermans, Jan N. M. Wilting, Saskia M. A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer |
title | A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer |
title_full | A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer |
title_fullStr | A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer |
title_full_unstemmed | A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer |
title_short | A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer |
title_sort | panel of dna methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637568/ https://www.ncbi.nlm.nih.gov/pubmed/34510716 http://dx.doi.org/10.1002/1878-0261.13098 |
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