Novel epigenetic markers for gastric cancer risk stratification in individuals after Helicobacter pylori eradication.
Gastric Cancer
; 21(5): 745-755, 2018 09.
Article
en En
| MEDLINE
| ID: mdl-29427040
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
/
Biomarcadores de Tumor
/
Infecciones por Helicobacter
/
Epigénesis Genética
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Gastric Cancer
Asunto de la revista:
GASTROENTEROLOGIA
/
NEOPLASIAS
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón