Format

Send to

Choose Destination
Gastric Cancer. 2018 Sep;21(5):745-755. doi: 10.1007/s10120-018-0803-4. Epub 2018 Feb 9.

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

Author information

1
Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan. tushijim@ncc.go.jp.
2
Department of Gastrointestinal Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. tushijim@ncc.go.jp.
3
Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
4
Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
5
Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.
6
Third Department of Internal Medicine, University of Toyama, Toyama, Japan.
7
Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
8
Department of Gastrointestinal Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

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.

KEYWORDS:

Cancer risk marker; DNA methylation; Epigenetics; Gastric cancer; Helicobacter pylori

PMID:
29427040
DOI:
10.1007/s10120-018-0803-4

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center