Authors: Ryo Suzuki Eiichiro Yamamoto Masanori Nojima Reo Maruyama Hiroo Yamano Kenjiro Yoshikawa Tomoaki Kimura Taku Harada Masami Ashida Takeshi Niinuma Akiko Sato Katsuhiko Nosho Hiroyuki Yamamoto Masahiro Kai Tamotsu Sugai Kohzoh Imai Hiromu Suzuki Yasuhisa Shinomura
Publish Date: 2013/08/13
Volume: 49, Issue: 7, Pages: 1135-1144
Abstract
Metachronous gastric cancer GC can develop after endoscopic resection of GC and cannot be predicted based on clinical signature Aberrant DNA methylation in noncancerous gastric mucosa is strongly implicated in gastric carcinogenesis and could be a useful biomarker of GC risk We evaluated the clinical utility of DNA methylation as a biomarker of metachronous GC riskWe carried out scheduled followup endoscopy in 129 patients after curative endoscopic resection of GC Biopsy specimens were collected from noncancerous mucosa in the gastric antrum and body after which quantitative methylation analysis of miR34b/c SFRP1 SFRP2 SFRP5 DKK2 and DKK3 was carried out using bisulfite pyrosequencing The utility of the methylation for predicting the risk of metachronous GC development was assessed using Kaplan–Meier and Cox proportional hazards model analysesDuring the followup period 17 patients 13 developed metachronous GCs The cumulative incidence of metachronous GC was significantly higher among patients with elevated miR34b/c SFRP2 and DKK2 methylation in their gastric body MiR34b/c showed the strongest association with the risk of metachronous GC and the cumulative incidence of metachronous GC was much higher in the highmiR34b/cmethylation group than the lowmethylation group Multivariate analysis adjusted for age sex H pylori status and pathological findings showed miR34b/c methylation in gastric body to be an independent predictor of metachronous GC riskGastric cancer GC is a major cause of cancer mortality worldwide and its early detection and endoscopic resection are essential for reducing the incidences of invasion and metastasis and improving survival Endoscopic submucosal dissection ESD enables en bloc and histologically complete resection with no restriction on lesion size 1 2 3 4 Although this approach minimizes the recurrence rate and preserves the entire stomach and the patient’s quality of life metachronous GC develops in the remnant stomach in about 10–20 of patients after curative ESD 5 6 7 Consequently assessing the risk of metachronous GC after ESD is extremely important for early detection of subsequent GC and reduction of mortalityHelicobacter pylori H pylori infection plays an important role in gastric carcinogenesis 8 GCs are thought to arise from H pylorirelated gastritis and the severe mucosal atrophy and intestinal metaplasia it causes are associated with the development of metachronous GC Correspondingly eradicating H pylori after ESD reduces the likelihood of metachronous GC 9 However the individuals at high risk of developing metachronous GC cannot be predicted based on clinicopathological findings including H pylori status Thus identification of a molecular marker useful for predicting the risk of metachronous GC would be highly desirable
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