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The prognostic efficacy of cell-free DNA hypermethylation in colorectal cancer

Epigenetic alterations in colorectal cancer (CRC) cause important differences in the underlying tumor biology and aggressiveness. DNA hypermethylation is central for the development of CRC but the prognostic impact remains elusive. We aimed to assess the association between cell-free hypermethylated...

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Autores principales: Rasmussen, Simon Ladefoged, Krarup, Henrik Bygum, Sunesen, Kåre Gotschalck, Johansen, Martin Berg, Stender, Mogens Tornby, Pedersen, Inge Søkilde, Madsen, Poul Henning, Thorlacius-Ussing, Ole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805532/
https://www.ncbi.nlm.nih.gov/pubmed/29467946
http://dx.doi.org/10.18632/oncotarget.24097
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author Rasmussen, Simon Ladefoged
Krarup, Henrik Bygum
Sunesen, Kåre Gotschalck
Johansen, Martin Berg
Stender, Mogens Tornby
Pedersen, Inge Søkilde
Madsen, Poul Henning
Thorlacius-Ussing, Ole
author_facet Rasmussen, Simon Ladefoged
Krarup, Henrik Bygum
Sunesen, Kåre Gotschalck
Johansen, Martin Berg
Stender, Mogens Tornby
Pedersen, Inge Søkilde
Madsen, Poul Henning
Thorlacius-Ussing, Ole
author_sort Rasmussen, Simon Ladefoged
collection PubMed
description Epigenetic alterations in colorectal cancer (CRC) cause important differences in the underlying tumor biology and aggressiveness. DNA hypermethylation is central for the development of CRC but the prognostic impact remains elusive. We aimed to assess the association between cell-free hypermethylated DNA and stage and survival in colorectal cancer (CRC). We analyzed pre-treatment plasma samples from 193 patients with CRC. Thirty gene-promoter regions were analyzed using methylation specific PCR. We compared the median number (range) of hypermethylated promoter regions with CRC stage, and constructed a multivariable Cox-regression model adjusted for stage, to evaluate the added prognostic information. The median number of hypermethylated promoter regions was nine (0-28) in patients with distant metastasis compared to five (0-19) in patients without metastatic disease (p < 0.0001). The majority of the hypermethylated promoter regions inferred a poor prognosis. Cox-regression analysis adjusted for patient age, sex, pre-treatment CEA-levels, and disease stage, showed that RARB (HR = 1.99, 95% CI [1.07, 3.72]) and RASSF1A (HR = 3.35, 95% CI [1.76, 6.38]) hypermethylation inferred a significant effect on survival. The risk of metastasis increase with the number of cell-free hypermethylated promoter regions. The presence of RARB and RASSF1A hypermethylation indicated aggressive disease, regardless of stage at the time of diagnosis.
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spelling pubmed-58055322018-02-21 The prognostic efficacy of cell-free DNA hypermethylation in colorectal cancer Rasmussen, Simon Ladefoged Krarup, Henrik Bygum Sunesen, Kåre Gotschalck Johansen, Martin Berg Stender, Mogens Tornby Pedersen, Inge Søkilde Madsen, Poul Henning Thorlacius-Ussing, Ole Oncotarget Research Paper Epigenetic alterations in colorectal cancer (CRC) cause important differences in the underlying tumor biology and aggressiveness. DNA hypermethylation is central for the development of CRC but the prognostic impact remains elusive. We aimed to assess the association between cell-free hypermethylated DNA and stage and survival in colorectal cancer (CRC). We analyzed pre-treatment plasma samples from 193 patients with CRC. Thirty gene-promoter regions were analyzed using methylation specific PCR. We compared the median number (range) of hypermethylated promoter regions with CRC stage, and constructed a multivariable Cox-regression model adjusted for stage, to evaluate the added prognostic information. The median number of hypermethylated promoter regions was nine (0-28) in patients with distant metastasis compared to five (0-19) in patients without metastatic disease (p < 0.0001). The majority of the hypermethylated promoter regions inferred a poor prognosis. Cox-regression analysis adjusted for patient age, sex, pre-treatment CEA-levels, and disease stage, showed that RARB (HR = 1.99, 95% CI [1.07, 3.72]) and RASSF1A (HR = 3.35, 95% CI [1.76, 6.38]) hypermethylation inferred a significant effect on survival. The risk of metastasis increase with the number of cell-free hypermethylated promoter regions. The presence of RARB and RASSF1A hypermethylation indicated aggressive disease, regardless of stage at the time of diagnosis. Impact Journals LLC 2018-01-09 /pmc/articles/PMC5805532/ /pubmed/29467946 http://dx.doi.org/10.18632/oncotarget.24097 Text en Copyright: © 2018 Rasmussen et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Rasmussen, Simon Ladefoged
Krarup, Henrik Bygum
Sunesen, Kåre Gotschalck
Johansen, Martin Berg
Stender, Mogens Tornby
Pedersen, Inge Søkilde
Madsen, Poul Henning
Thorlacius-Ussing, Ole
The prognostic efficacy of cell-free DNA hypermethylation in colorectal cancer
title The prognostic efficacy of cell-free DNA hypermethylation in colorectal cancer
title_full The prognostic efficacy of cell-free DNA hypermethylation in colorectal cancer
title_fullStr The prognostic efficacy of cell-free DNA hypermethylation in colorectal cancer
title_full_unstemmed The prognostic efficacy of cell-free DNA hypermethylation in colorectal cancer
title_short The prognostic efficacy of cell-free DNA hypermethylation in colorectal cancer
title_sort prognostic efficacy of cell-free dna hypermethylation in colorectal cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805532/
https://www.ncbi.nlm.nih.gov/pubmed/29467946
http://dx.doi.org/10.18632/oncotarget.24097
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