TY - JOUR
T1 - DNA methylation accumulation in gastric mucosa adjacent to cancer after Helicobacter pylori eradication
AU - Tahara, Sayumi
AU - Tahara, Tomomitsu
AU - Horiguchi, Noriyuki
AU - Kato, Takema
AU - Shinkai, Yasuko
AU - Yamashita, Hiromi
AU - Yamada, Hyuga
AU - Kawamura, Tomohiko
AU - Terada, Tsuyoshi
AU - Okubo, Masaaki
AU - Nagasaka, Mitsuo
AU - Nakagawa, Yoshihito
AU - Shibata, Tomoyuki
AU - Yamada, Seiji
AU - Urano, Makoto
AU - Tsukamoto, Tetsuya
AU - Kurahashi, Hiroki
AU - Kuroda, Makoto
AU - Ohmiya, Naoki
N1 - Publisher Copyright:
© 2018 UICC
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85056478287&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056478287&partnerID=8YFLogxK
U2 - 10.1002/ijc.31667
DO - 10.1002/ijc.31667
M3 - Article
C2 - 29978464
AN - SCOPUS:85056478287
SN - 0020-7136
VL - 144
SP - 80
EP - 88
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 1
ER -