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Normal gastric mucosa from gastric cancer cases and healthy controls exhibit methylome-wide changes associated with current and past Helicobacter pylori infection and cancer risk

ABSTRACT: Aim: We aimed to investigate the impact of H. pylori on the epigenome in normal gastric mucosa and whether these changes constitute cancer risk. Method: The Infinium HumanMethylation450 BeadChip Kit was used to assess methylation Results: We found 1924 differentially methylated positions (DMPs) and 438 differentially methylated regions (DMRs) associated with H. pylori infection, most of which were hypermethylated. Significant methylation alterations identified in the initial sample set were replicated in a second validation set. The H. pylori-associated DMP/Rs showed marked stability after H. pylori clearance. Furthermore, we found 152 DMRs associated with cancer risk, regardless of H. pylori status. A methylation score derived using three biomarkers was a strong predictor of GC, with an area under the curve of 0.765.

ORGANISM(S): Homo sapiens

PROVIDER: GSE99553 | GEO | 2017/08/30

SECONDARY ACCESSION(S): PRJNA388961

REPOSITORIES: GEO

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Project description:To further our understanding of the role of DNA methylation in development, Methylated DNA Immunoprecipitation (MeDIP) was used in conjunction with a NimbleGen promoter plus CpG island array to identify Tissue and Developmental Stage specific Differentially Methylated DNA Regions (T-DMRs and DS-DMRs) on a genome-wide basis. Four tissues (brain, heart, liver, and testis) from C57BL/6J mice were analyzed at three developmental stages (15 day embryo, E15; new born, NB; 12 week adult, AD). Almost 5,000 adult T-DMRs and 10,000 DS-DMRs were identified. Surprisingly, almost all DS-DMRs were tissue specific (i.e., methylated and ummenthylated in one or more non-overlapping tissues), indicating that the vast majority of unique sequence DNA methylation has tissue specificity. Also, many DS-DMRs were methylated at early development stages (E15 and NB) but unmethylated in adult, indicating “demethylation” has a prominent role in tissue differentiation. The pattern of DNA methylation in adult testis was dramatically different from somatic tissues in many aspects, mostly notably with a very strong bias of methylation in non-CpGi (CpG island) promoter regions (94%). Although the majority of T-DMRs and DS-DMRs tended to be in non-CpGi promoter regions, a relatively large number were also located in CpGi in promoter, intra-genic and inter-genic regions (>15% of all CpGi). Gene Ontology analysis of genes with methylation in non-CpGi promoters indicates enrichment of genes related to membrane proteins and G-protein coupled receptors. Our data also suggest regulatory roles of DNA methylation outside of promoter regions and in alternative promoter selection. Overall, our studies indicate that change in DNA methylation during development is a dynamic, widespread and tissue-specific process involving both DNA methylation and demethylation. Comparison of DNA methylation across 3 developmental stages (15 day embryo, newborn, and adult) for four tissues (brain, heart, liver and testis)

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Normal gastric mucosa from gastric cancer cases and healthy controls exhibit methylome-wide changes associated with current and past Helicobacter pylori infection and cancer risk

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