Ndrg2 promoter hypermethylation triggered by helicobacter pylori infection correlates with poor patients survival in human gastric carcinoma
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Zhi-Qiang Ling1, Ming-Hua Ge2, Xiao-Xiao Lu1, Jin Han1, Yi-Chen Wu1, Xiang Liu1, Xin Zhu1 and Lian-Lian Hong1
1 Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China
2 Department of Tumor Surgery, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China
Zhi-Qiang Ling, email:
Keywords: gastric carcinoma, Helicobacter pylori (H. pylori) infection, DNMT3b, N-myc downstream regulated gene 2 (Ndrg2), promoter methylation
Received: September 20, 2014 Accepted: February 03, 2015 Published: March 15, 2015
N-myc downstream regulated gene 2 (Ndrg2) is a candidate suppressor of cancer metastasis. We found that Ndrg2 promoter was frequently hypermethylated in gastric cancer cell lines and in 292 gastric tumor tissues. This resulted in down-regulation of Ndrg2 mRNA and protein. Ndrg2 promoter methylation was associated with H. pylori infection and worse prognosis of gastric cancer patients, which is an independent prognostic factor for the disease-free survival (DFS). We found that H. pylori silenced Ndrg2 by activating the NF-κB pathway and up-regulating DNMT3b, promoting gastric cancer progression. These findings uncover a previously unrecognized role for H. pylori infection in gastric cancer.
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