Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Sep 28, 2012; 18(36): 5129-5134
Published online Sep 28, 2012. doi: 10.3748/wjg.v18.i36.5129
CpG island methylator phenotype and Helicobacter pylori infection associated with gastric cancer
Ji-Bin Liu, Xu-Ming Wu, Jin Cai, Jin-Ye Zhang, Jin-Lin Zhang, Shu-Hui Zhou, Min-Xin Shi, Fu-Lin Qiang
Ji-Bin Liu, Xu-Ming Wu, Jin Cai, Jin-Ye Zhang, Jin-Lin Zhang, Min-Xin Shi, Fu-Lin Qiang, Tumor Institute, Nantong Tumor Hospital, Nantong 226361, Jiangsu Province, China
Shu-Hui Zhou, School of Radiology and Public Health, Soochow University, Suzhou 215123, Jiangsu Province, China
Author contributions: Liu JB and Wu XM contributed equally to this work; Liu JB and Qiang FL designed the study, performed data analysis and interpretation; Cai J, Zhang JY and Zhang JL critically revised the manuscript for intellectual content; Wu XM and Zhou SH performed the statistical analysis; Shi MX was responsible for data acquisition.
Supported by Department of Health of Jiangsu Province of China, No. H200957
Correspondence to: Dr. Fu-Lin Qiang, Tumor Institute, Nantong Tumor Hospital, 30 Tongyang Beilu, Pingchao Town, Nantong 226361, Jiangsu Province, China. doctorjibinliu@163.com
Telephone: +86-513-86729067 Fax: +86-513-86571201
Received: August 1, 2011
Revised: April 16, 2012
Accepted: August 15, 2012
Published online: September 28, 2012
Abstract

AIM: To investigate the association between the CpG island methylator phenotype (CIMP) and serum Helicobacter pylori (H. pylori) levels for clinical prediction of gastric cancer (GC) progression.

METHODS: We analyzed the serum CIMP status of 75 patients with GC using a methylation marker panel and a methylation-specific polymerase chain reaction. Serum samples from 40 healthy persons were examined at the same time. The genes examined were APC, WIF-1, RUNX-3, DLC-1, SFRP-1, DKK and E-cad. H. pylori infection in serum was assayed with an anti-H. pylori immunoglobulin G antibody test and a rapid urease test.

RESULTS: The frequencies of high-level methylation in GC tissues for the seven genes were: 48% for APC, 57.33% for WIF-1, 56% for RUNX-3, 50.67% for DLC-1, 52% for SFRP-1, 54.67% for DKK, and 48% for E-cad. The frequencies in GC serum were 30.67% for APC, 34.67% for WIF-1, 37.33% for RUNX-3, 29.33% for DLC-1, 33.33% for SFRP-1, 32% for DKK, and 26.67% for E-cad. CIMP+ (defined as ≥ 3 methylated genes) was associated with 47 (62.67%) GC tissue samples and 44 (58.67%) GC serum samples. CIMP+ was not associated with non-neoplastic mucosal tissues or the serum of healthy persons. Of the 75 GC cases, 51 (68%) were H. pylori+, and 24 (32%) were H. pylori-. Of the 51 H. pylori+ cases, 36 were CIMP+ and 15 were CIMP-. In contrast, for the 24 H. pylori- cases, 11 were CIMP+, and 13 were CIMP-. The difference was significant between the H. pylori+ and H. pylori- groups (χ2 = 4.27, P < 0.05). Of the 51 H. pylori+ GC patients, 34 were CIMP+ and 17 were CIMP-, while among the 24 H. pylori- GC cases, 10 were CIMP+ and 14 were CIMP-. The difference was significant between the H. pylori+ and H. pylori- groups (χ2 = 4.21, P < 0.05). A 2-year follow-up showed significant difference in the rates of metastasis and recurrence between H. pylori+/CIMP+ cases and the H. pylori+/CIMP- cases or CIMP- cases associated with H. pylori assayed in serum (P < 0.05). However, there were no significant differences in survival rates between the two groups.

CONCLUSION: H. pylori+/CIMP+ cases are associated with higher rates of metastasis and recurrence than H. pylori+/CIMP- cases. Serum may be useful for examining CIMP status.

Keywords: CpG island methylator phenotype; Helicobacter pylori; Serum; Prognosis; Gastric cancer