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Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer

Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methyla...

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Autores principales: Swets, Marloes, Zaalberg, Anniek, Boot, Arnoud, van Wezel, Tom, Frouws, Martine A., Bastiaannet, Esther, Gelderblom, Hans, van de Velde, Cornelis J. H., Kuppen, Peter J. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297671/
https://www.ncbi.nlm.nih.gov/pubmed/28035987
http://dx.doi.org/10.3390/ijms18010036
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author Swets, Marloes
Zaalberg, Anniek
Boot, Arnoud
van Wezel, Tom
Frouws, Martine A.
Bastiaannet, Esther
Gelderblom, Hans
van de Velde, Cornelis J. H.
Kuppen, Peter J. K.
author_facet Swets, Marloes
Zaalberg, Anniek
Boot, Arnoud
van Wezel, Tom
Frouws, Martine A.
Bastiaannet, Esther
Gelderblom, Hans
van de Velde, Cornelis J. H.
Kuppen, Peter J. K.
author_sort Swets, Marloes
collection PubMed
description Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03–2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13–3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated.
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spelling pubmed-52976712017-02-10 Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer Swets, Marloes Zaalberg, Anniek Boot, Arnoud van Wezel, Tom Frouws, Martine A. Bastiaannet, Esther Gelderblom, Hans van de Velde, Cornelis J. H. Kuppen, Peter J. K. Int J Mol Sci Article Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03–2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13–3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated. MDPI 2016-12-27 /pmc/articles/PMC5297671/ /pubmed/28035987 http://dx.doi.org/10.3390/ijms18010036 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Swets, Marloes
Zaalberg, Anniek
Boot, Arnoud
van Wezel, Tom
Frouws, Martine A.
Bastiaannet, Esther
Gelderblom, Hans
van de Velde, Cornelis J. H.
Kuppen, Peter J. K.
Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer
title Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer
title_full Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer
title_fullStr Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer
title_full_unstemmed Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer
title_short Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer
title_sort tumor line-1 methylation level in association with survival of patients with stage ii colon cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297671/
https://www.ncbi.nlm.nih.gov/pubmed/28035987
http://dx.doi.org/10.3390/ijms18010036
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