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01-09-2018 | Original Article

Novel epigenetic markers for gastric cancer risk stratification in individuals after Helicobacter pylori eradication

Authors: Masahiro Maeda, Satoshi Yamashita, Taichi Shimazu, Naoko Iida, Hideyuki Takeshima, Takeshi Nakajima, Ichiro Oda, Sohachi Nanjo, Chika Kusano, Akiko Mori, Hiroshi Moro, Harumi Yamada, Shoichiro Tsugane, Toshiro Sugiyama, Yoshiharu Sakai, Toshikazu Ushijima

Published in: Gastric Cancer | Issue 5/2018

Abstract

Background

The risk stratification of healthy individuals after Helicobacter pylori eradication is an urgent issue. The assessment of aberrant DNA methylation accumulated in gastric tissues with normal appearance, which can reflect overall epigenomic damage, is a promising strategy. We aimed to establish novel epigenetic cancer risk markers for H. pylori-eradicated individuals.

Methods

Gastric mucosa was collected from eight healthy volunteers without H. pylori infection (G1), 75 healthy individuals with gastric atrophy (G2), and 94 gastric cancer patients (G3) after H. pylori eradication. Genome-wide analysis was conducted using Infinium 450 K and differentially methylated probes were screened using large difference and iEVORA-based methods. Bisulfite pyrosequencing was used for validation.

Results

Screening, using 8 G1, 12 G2, and 12 G3 samples, isolated 57 candidates unmethylated in G1 and differentially methylated in G3 compared with G2. Validation for nine candidate markers (FLT3, LINC00643, RPRM, JAM2, ELMO1, BHLHE22, RIMS1, GUSBP5, and ZNF3) in 63 G2 and 82 G3 samples showed that all of them had significantly higher methylation levels in G3 than in G2 (P < 0.0001). Their methylation levels were highly correlated, which indicated that they reflect overall epigenomic damage. The candidates had sufficient performance (AUC: 0.70–0. 80) and high odds ratios (5.43–23.41), some of which were superior to a previous marker, miR-124a-3. The methylation levels of our novel markers were not associated with gastric atrophy, gender, or age.

Conclusions

Novel epigenetic markers for gastric cancer risk optimized for H. pylori-eradicated individuals were established.

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Title: Novel epigenetic markers for gastric cancer risk stratification in individuals after Helicobacter pylori eradication
Authors: Masahiro Maeda
Satoshi Yamashita
Taichi Shimazu
Naoko Iida
Hideyuki Takeshima
Takeshi Nakajima
Ichiro Oda
Sohachi Nanjo
Chika Kusano
Akiko Mori
Hiroshi Moro
Harumi Yamada
Shoichiro Tsugane
Toshiro Sugiyama
Yoshiharu Sakai
Toshikazu Ushijima
Publication date: 01-09-2018
Publisher: Springer Japan
Published in: Gastric Cancer / Issue 5/2018
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI: https://doi.org/10.1007/s10120-018-0803-4

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