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Int. J. Mol. Sci. 2017, 18(1), 36; doi:10.3390/ijms18010036

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

1
Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
2
Department of Clinical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
3
Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editor: Stephen A. Bustin
Received: 22 November 2016 / Revised: 17 December 2016 / Accepted: 19 December 2016 / Published: 27 December 2016
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Abstract

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. View Full-Text
Keywords: stage II colon cancer; LINE-1; methylation; biomarker stage II colon cancer; LINE-1; methylation; biomarker
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Swets, M.; Zaalberg, A.; Boot, A.; van Wezel, T.; Frouws, M.A.; Bastiaannet, E.; Gelderblom, H.; van de Velde, C.J.H.; Kuppen, P.J.K. Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer. Int. J. Mol. Sci. 2017, 18, 36.

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