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A prognostic CpG score derived from epigenome-wide profiling of tumor tissue was independently associated with colorectal cancer survival

BACKGROUND: Results of previous studies on the association of the CpG island methylator phenotype (CIMP) with colorectal cancer (CRC) prognosis were inconsistent and mostly based on different CIMP definitions. The current study aimed to comprehensively investigate the associations between DNA methyl...

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Autores principales: Jia, Min, Zhang, Yan, Jansen, Lina, Walter, Viola, Edelmann, Dominic, Gündert, Melanie, Tagscherer, Katrin E., Roth, Wilfried, Bewerunge-Hudler, Melanie, Herpel, Esther, Kloor, Matthias, Ulrich, Alexis, Burwinkel, Barbara, Bläker, Hendrik, Chang-Claude, Jenny, Brenner, Hermann, Hoffmeister, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657180/
https://www.ncbi.nlm.nih.gov/pubmed/31340858
http://dx.doi.org/10.1186/s13148-019-0703-4
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author Jia, Min
Zhang, Yan
Jansen, Lina
Walter, Viola
Edelmann, Dominic
Gündert, Melanie
Tagscherer, Katrin E.
Roth, Wilfried
Bewerunge-Hudler, Melanie
Herpel, Esther
Kloor, Matthias
Ulrich, Alexis
Burwinkel, Barbara
Bläker, Hendrik
Chang-Claude, Jenny
Brenner, Hermann
Hoffmeister, Michael
author_facet Jia, Min
Zhang, Yan
Jansen, Lina
Walter, Viola
Edelmann, Dominic
Gündert, Melanie
Tagscherer, Katrin E.
Roth, Wilfried
Bewerunge-Hudler, Melanie
Herpel, Esther
Kloor, Matthias
Ulrich, Alexis
Burwinkel, Barbara
Bläker, Hendrik
Chang-Claude, Jenny
Brenner, Hermann
Hoffmeister, Michael
author_sort Jia, Min
collection PubMed
description BACKGROUND: Results of previous studies on the association of the CpG island methylator phenotype (CIMP) with colorectal cancer (CRC) prognosis were inconsistent and mostly based on different CIMP definitions. The current study aimed to comprehensively investigate the associations between DNA methylation on genes previously used to define CIMP status with CRC survival. RESULTS: Patients with CRC followed up for a median of 5.2 years were divided into a study cohort (n = 568) and a validation cohort (n = 308). DNA methylation was measured in tumor tissue using the Illumina Infinium HumanMethylation450 BeadChip and restricted to 43 genes used to define CIMP status in previous studies. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) of survival after CRC, including adjustment for tumor stage, microsatellite instability, and BRAF mutation status. In the study cohort, ten CpG sites were identified to be associated with CRC survival. Seven of these ten CpG sites were also associated with CRC survival in the validation cohort and were used to construct a prognostic score. CRC patients with a prognostic score of the lowest methylation level showed poorer disease-specific survival compared with patients with the highest methylation level in both the study cohort and the validation cohort (HR = 3.11 and 95% CI = 1.97–4.91, and HR = 3.06 and 95% CI = 1.71–5.45, respectively). CONCLUSIONS: A CpG panel consisting of seven CpG sites was found to be strongly associated with CRC survival, independent from important clinical factors and mutations associated with CIMP. Further studies are required to confirm these findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-019-0703-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-66571802019-07-31 A prognostic CpG score derived from epigenome-wide profiling of tumor tissue was independently associated with colorectal cancer survival Jia, Min Zhang, Yan Jansen, Lina Walter, Viola Edelmann, Dominic Gündert, Melanie Tagscherer, Katrin E. Roth, Wilfried Bewerunge-Hudler, Melanie Herpel, Esther Kloor, Matthias Ulrich, Alexis Burwinkel, Barbara Bläker, Hendrik Chang-Claude, Jenny Brenner, Hermann Hoffmeister, Michael Clin Epigenetics Research BACKGROUND: Results of previous studies on the association of the CpG island methylator phenotype (CIMP) with colorectal cancer (CRC) prognosis were inconsistent and mostly based on different CIMP definitions. The current study aimed to comprehensively investigate the associations between DNA methylation on genes previously used to define CIMP status with CRC survival. RESULTS: Patients with CRC followed up for a median of 5.2 years were divided into a study cohort (n = 568) and a validation cohort (n = 308). DNA methylation was measured in tumor tissue using the Illumina Infinium HumanMethylation450 BeadChip and restricted to 43 genes used to define CIMP status in previous studies. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) of survival after CRC, including adjustment for tumor stage, microsatellite instability, and BRAF mutation status. In the study cohort, ten CpG sites were identified to be associated with CRC survival. Seven of these ten CpG sites were also associated with CRC survival in the validation cohort and were used to construct a prognostic score. CRC patients with a prognostic score of the lowest methylation level showed poorer disease-specific survival compared with patients with the highest methylation level in both the study cohort and the validation cohort (HR = 3.11 and 95% CI = 1.97–4.91, and HR = 3.06 and 95% CI = 1.71–5.45, respectively). CONCLUSIONS: A CpG panel consisting of seven CpG sites was found to be strongly associated with CRC survival, independent from important clinical factors and mutations associated with CIMP. Further studies are required to confirm these findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-019-0703-4) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-24 /pmc/articles/PMC6657180/ /pubmed/31340858 http://dx.doi.org/10.1186/s13148-019-0703-4 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Jia, Min
Zhang, Yan
Jansen, Lina
Walter, Viola
Edelmann, Dominic
Gündert, Melanie
Tagscherer, Katrin E.
Roth, Wilfried
Bewerunge-Hudler, Melanie
Herpel, Esther
Kloor, Matthias
Ulrich, Alexis
Burwinkel, Barbara
Bläker, Hendrik
Chang-Claude, Jenny
Brenner, Hermann
Hoffmeister, Michael
A prognostic CpG score derived from epigenome-wide profiling of tumor tissue was independently associated with colorectal cancer survival
title A prognostic CpG score derived from epigenome-wide profiling of tumor tissue was independently associated with colorectal cancer survival
title_full A prognostic CpG score derived from epigenome-wide profiling of tumor tissue was independently associated with colorectal cancer survival
title_fullStr A prognostic CpG score derived from epigenome-wide profiling of tumor tissue was independently associated with colorectal cancer survival
title_full_unstemmed A prognostic CpG score derived from epigenome-wide profiling of tumor tissue was independently associated with colorectal cancer survival
title_short A prognostic CpG score derived from epigenome-wide profiling of tumor tissue was independently associated with colorectal cancer survival
title_sort prognostic cpg score derived from epigenome-wide profiling of tumor tissue was independently associated with colorectal cancer survival
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657180/
https://www.ncbi.nlm.nih.gov/pubmed/31340858
http://dx.doi.org/10.1186/s13148-019-0703-4
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