{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T20:35:57Z","timestamp":1774038957753,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2012,5,10]],"date-time":"2012-05-10T00:00:00Z","timestamp":1336608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2012,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p><jats:italic>Helicobacter pylori<\/jats:italic> has been recognized as a definite carcinogen for gastric cancer (GC); however, the pathogenesis of <jats:italic>H. pylori<\/jats:italic> infection remains unclear. Runt\u2010related transcription factor 3 (<jats:italic>RUNX3<\/jats:italic>) is a candidate tumor suppressor gene whose deficiency is causally related to GC. However, in <jats:italic>H. pylori<\/jats:italic> infection\u2010associated GC, the role of <jats:italic>RUNX3<\/jats:italic> has not been studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>The authors used real\u2010time methylation\u2010specific polymerase chain reaction analysis to determine methylation status of the <jats:italic>RUNX3<\/jats:italic> 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 <jats:italic>RUNX3<\/jats:italic> methylation and <jats:italic>H. pylori<\/jats:italic> infection, and the concordance of methylation levels was investigated between serum and tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>The results indicated that increasing <jats:italic>RUNX3<\/jats:italic> 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%). <jats:italic>H. pylori<\/jats:italic> infection, a major risk factor for GC, contributed to the inactivation of <jats:italic>RUNX3<\/jats:italic> in gastric epithelial cells through promoter hypermethylation. The levels of <jats:italic>RUNX3<\/jats:italic> methylation in serum were in significant concordance with the methylation levels observed in GC tissues (<jats:italic>P<\/jats:italic> = .887).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>The current findings supported <jats:italic>RUNX3<\/jats:italic> methylation as a risk factors for the carcinogenesis of chronic atrophic gastritis with <jats:italic>H. pylori<\/jats:italic> infection and indicated that circulating <jats:italic>RUNX3<\/jats:italic> methylation is a valuable biomarker for the detection of early GC. Cancer 2012. \u00a9 2012 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.27604","type":"journal-article","created":{"date-parts":[[2012,5,10]],"date-time":"2012-05-10T11:34:53Z","timestamp":1336649693000},"page":"5507-5517","source":"Crossref","is-referenced-by-count":65,"title":["Stepwise cumulation of <i>RUNX3<\/i> methylation mediated by <i>Helicobacter pylori<\/i> infection contributes to gastric carcinoma 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