title: Stepwise cumulation of RUNX3 methylation mediated by Helicobacter pylori infection contributes to gastric carcinoma progression.
abstract: BACKGROUND
  Helicobacter pylori has been recognized as a definite carcinogen for gastric cancer (GC); however, the pathogenesis of H. pylori infection remains unclear. Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene whose deficiency is causally related to GC. However, in H. pylori infection-associated GC, the role of RUNX3 has not been studied.
  
  
  METHODS
  The authors used real-time methylation-specific polymerase chain reaction analysis to determine methylation status of the RUNX3 promoter in a spectrum of gastric lesions, including 220 samples of chronic atrophic gastritis, 196 samples of intestinal metaplasia, 134 samples of gastric adenoma, 102 samples of dysplasia, and 202 samples of GC with paired noncancerous mucosa tissues and corresponding blood specimens. The association of abnormal methylation with precancerous gastric lesions was evaluated along with the association between RUNX3 methylation and H. pylori infection, and the concordance of methylation levels was investigated between serum and tissues.
  
  
  RESULTS
  The results indicated that increasing RUNX3 promoter methylation was correlated with distinct stages of GC progression. GC tissues had the highest methylation proportion (75.2%) compared with precancerous gastric lesions, including chronic atrophic gastritis (15.9%), intestinal metaplasia (36.7%), gastric adenoma (41.8%), and dysplasia (54.9%). H. pylori infection, a major risk factor for GC, contributed to the inactivation of RUNX3 in gastric epithelial cells through promoter hypermethylation. The levels of RUNX3 methylation in serum were in significant concordance with the methylation levels observed in GC tissues (P = .887).
  
  
  CONCLUSIONS
  The current findings supported RUNX3 methylation as a risk factors for the carcinogenesis of chronic atrophic gastritis with H. pylori infection and indicated that circulating RUNX3 methylation is a valuable biomarker for the detection of early GC.
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, People's Republic of China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Lu
authors.forename: Jiang-Liu
authors.initials: JL
authors.lastname: Yu
authors.forename: Li-Sha
authors.initials: LS
authors.lastname: Ying
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.forename: Shi
authors.initials: S
authors.lastname: Wang
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Yu
authors.forename: Xin-Bao
authors.initials: XB
authors.lastname: Wang
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Fang
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Ling
mesh_terms: D000236:Adenoma / Q000235:genetics; D000328:Adult; D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D050677:Core Binding Factor Alpha 3 Subunit / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa; D005757:Gastritis, Atrophic / Q000235:genetics; D016481:Helicobacter Infections / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008679:Metaplasia / Q000235:genetics; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human