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Gastric Cancer
Published in: Gastric Cancer 4/2013

Open Access 01-10-2013 | Original Article

LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis

Authors: Hironobu Shigaki, Yoshifumi Baba, Masayuki Watanabe, Asuka Murata, Shiro Iwagami, Keisuke Miyake, Takatsugu Ishimoto, Masaaki Iwatsuki, Hideo Baba

Published in: Gastric Cancer | Issue 4/2013

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Abstract

Background

Genome-wide DNA hypomethylation plays an important role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level. In some types of human neoplasms, LINE-1 methylation level is attracting interest as a predictive marker for patient prognosis. However, the prognostic significance of LINE-1 hypomethylation in gastric cancer remains unclear.

Methods

Using 203 resected gastric cancer specimens, we quantified LINE-1 methylation using bisulfite-pyrosequencing technology. A Cox proportional hazards model was used to calculate the hazard ratio (HR), adjusted for the clinical and pathological variables.

Results

Gastric cancers showed significantly lower LINE-1 methylation levels compared to matched normal gastric mucosa (p < 0.0001; n = 74). Tumoral LINE-1 methylation range was 11.6–97.5 on a 0–100 scale (n = 203; mean 71.4, median 74.4, standard deviation 12.9). LINE-1 hypomethylation was significantly associated with shorter overall survival [log-rank p = 0.029; univariate HR 2.01, 95 % confidence interval (CI) 1.09–3.99, p = 0.023; stage-matched HR 1.88, 95 % CI 1.02–3.74, p = 0.041; multivariate HR 1.98, 95 % CI 1.04–4.04, p = 0.036]. No significant effect modification was observed by any of the covariates in survival analysis (all p interaction >0.25).

Conclusions

LINE-1 hypomethylation in gastric cancer is associated with shorter survival, suggesting that it has potential for use as a prognostic biomarker.
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Metadata
Title
LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis
Authors
Hironobu Shigaki
Yoshifumi Baba
Masayuki Watanabe
Asuka Murata
Shiro Iwagami
Keisuke Miyake
Takatsugu Ishimoto
Masaaki Iwatsuki
Hideo Baba
Publication date
01-10-2013
Publisher
Springer Japan
Published in
Gastric Cancer / Issue 4/2013
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-012-0209-7

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