DNA methylation accumulation in gastric mucosa adjacent to cancer after Helicobacter pylori eradication

Abstract

Molecular irreversibleness with Helicobacter pylori (H. pylori) infection might have a role in gastric tumorigenesis after H. pylori eradication. We performed comprehensive DNA methylation profiling of gastric mucosa after H. pylori eradication with or without gastric cancer. Using four different groups of biopsies obtained from gastric body without history of H. pylori infection (Hp-), gastric body without cancer after H. pylori eradication (cancer-free body), gastric body with early gastric cancer diagnosed after H. pylori eradication (EGC body) and their paired samples from adjacent mucosa of cancer (EGC ADJ), methylation status of five candidate genes (MYOD1, SLC16A12, IGF2, RORA and PRDM5) was examined by the bisulfite pyrosequencing. An Infinium Methylation EPIC BeadChip array was also used to characterize the methylation status of greater than 850,000 CpG sites. The EGC ADJ group showed highest methylation levels of five candidate genes among the four groups of biopsies. In the gastric body (cancer-free body + EGC body), methylation levels were significantly decreased in patients with longer period after eradication, while such association was not observed in EGC ADJ group. Hyper methylated samples were associated with shorter telomere, an indicator for rapid cell turnover, and higher DNMT1 protein expression, an enzyme related to methyl transfer reaction. The genome-wide methylation analysis demonstrated strikingly higher methylation levels especially at CpG islands in the EGC ADJ group. Exclusively hypermethylated promoter CpG islands in the same group frequently coded zinc finger proteins. Our data show that DNA methylation accumulation is associated with molecular irreversibleness and gastric carcinogenesis after H. pylori eradication.

DNA hypomethylation-related overexpression of SFN, GORASP2 and ZYG11A is a novel prognostic biomarker for early stage lung adenocarcinoma

“…One of the methods to find differentially methylated genes is using Infinium methylation array [20]. Methylation array using the Infinium MethylationEPIC Bead Chip microarray (Illumina) analyzed more than 850,000 CpG sites covering 99% of the Refseq genes [21]. For further processing we used the MACON web tool.…”

Characteristics and Early Diagnosis of Gastric Cancer Discovered after Helicobacter pylori Eradication

“…Recently, a molecular marker associated with DNA methylation has been investigated, and we hope a possible marker for the risk stratification and may be applied for these subjects in the near future. [66][67][68][69]…”

Epigenome-wide DNA methylation profiling of portal vein tumor thrombosis (PVTT) tissues in hepatocellular carcinoma patients

“…Aberrant DNA methylation status has emerged as an important hallmark in various cancers [4] . Abnormal methylation of tumor suppressor genes and oncogenes has been proven to play an important role in many malignancies, such as liver cancer [5] , [6] , [7] , [8] , [9] , gastric cancer [10] and colorectal cancer [11] , [12] . DNA methylation is a dynamic epigenetic marker accompanied with occurrence and development of cancer, which has widely effects on the prevention, diagnosis, prediction and therapy of the disease [13] .…”