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Ndrg2 promoter hypermethylation triggered by helicobacter pylori infection correlates with poor patients survival in human gastric carcinoma.

Ling ZQ, Ge MH, Lu XX, Han J, Wu YC, Liu X, Zhu X, Hong LL - Oncotarget (2015)

Bottom Line: 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.We found that H. pylori silenced Ndrg2 by activating the NF-κB pathway and up-regulating DNMT3b, promoting gastric cancer progression.

View Article: PubMed Central - PubMed

Affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Correlation of Ndrg2 methylation level with survival of patients with gastric cancerA: Kaplan-Meier curves of overall disease-free survival (DFS) in patients with gastric cancer treated with primary gastrectomy according to the methylated level of Ndrg2. B: Kaplan-Meier curves of overall survival (OS) in patients with gastric cancer treated with primary gastrectomy according to the methylated level of Ndrg2.
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Figure 4: Correlation of Ndrg2 methylation level with survival of patients with gastric cancerA: Kaplan-Meier curves of overall disease-free survival (DFS) in patients with gastric cancer treated with primary gastrectomy according to the methylated level of Ndrg2. B: Kaplan-Meier curves of overall survival (OS) in patients with gastric cancer treated with primary gastrectomy according to the methylated level of Ndrg2.

Mentions: We next investigated the association of Ndrg2 methylation with patient survival. We analyzed both disease-free survival (DFS) and overall survival (OS). In both situations, Ndrg2 methylation is significantly associated with poorer prognosis; shorter DFS and lower OS. The average durations of DFS and OS in patients with Ndrg2 methylation in the tumors (Methylation score = 1-4) were significantly shorter than those of patients without Ndrg2 methylation in the tumors (Figure 4). The average DFS in patients with Ndrg2 methylation was 24.9 months vs 53.2 months in patients without Ndrg2 methylation. The average OS in patients with Ndrg2 methylation was 40.6 months vs 59.3 months in patients without Ndrg2 methylation (Table 2). Ndrg2 methylation was strongly associated with late stage tumors, but the association of Ndrg2 methylation level with patient survival is independent on the tumor stage (Supplementary Figure 2). In addition to Ndrg2 methylation, we observed that a number of other previously characterized clinical parameters were associated with patient survival (Table 2), including age at diagnosis, H. pylori infection, tumor size, differentiation, venous invasion, lymphatic invasion, invasive depth, nodal metastasis, distant metastasis, and TNM stage. In summary, these data indicate that in addition to a majority of clinical characteristics that have been shown to affect prognosis of gastric cancer patients, the methylation level of Ndrg2 might serve as an independent marker to predict the DFS of the patients.


Ndrg2 promoter hypermethylation triggered by helicobacter pylori infection correlates with poor patients survival in human gastric carcinoma.

Ling ZQ, Ge MH, Lu XX, Han J, Wu YC, Liu X, Zhu X, Hong LL - Oncotarget (2015)

Correlation of Ndrg2 methylation level with survival of patients with gastric cancerA: Kaplan-Meier curves of overall disease-free survival (DFS) in patients with gastric cancer treated with primary gastrectomy according to the methylated level of Ndrg2. B: Kaplan-Meier curves of overall survival (OS) in patients with gastric cancer treated with primary gastrectomy according to the methylated level of Ndrg2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480746&req=5

Figure 4: Correlation of Ndrg2 methylation level with survival of patients with gastric cancerA: Kaplan-Meier curves of overall disease-free survival (DFS) in patients with gastric cancer treated with primary gastrectomy according to the methylated level of Ndrg2. B: Kaplan-Meier curves of overall survival (OS) in patients with gastric cancer treated with primary gastrectomy according to the methylated level of Ndrg2.
Mentions: We next investigated the association of Ndrg2 methylation with patient survival. We analyzed both disease-free survival (DFS) and overall survival (OS). In both situations, Ndrg2 methylation is significantly associated with poorer prognosis; shorter DFS and lower OS. The average durations of DFS and OS in patients with Ndrg2 methylation in the tumors (Methylation score = 1-4) were significantly shorter than those of patients without Ndrg2 methylation in the tumors (Figure 4). The average DFS in patients with Ndrg2 methylation was 24.9 months vs 53.2 months in patients without Ndrg2 methylation. The average OS in patients with Ndrg2 methylation was 40.6 months vs 59.3 months in patients without Ndrg2 methylation (Table 2). Ndrg2 methylation was strongly associated with late stage tumors, but the association of Ndrg2 methylation level with patient survival is independent on the tumor stage (Supplementary Figure 2). In addition to Ndrg2 methylation, we observed that a number of other previously characterized clinical parameters were associated with patient survival (Table 2), including age at diagnosis, H. pylori infection, tumor size, differentiation, venous invasion, lymphatic invasion, invasive depth, nodal metastasis, distant metastasis, and TNM stage. In summary, these data indicate that in addition to a majority of clinical characteristics that have been shown to affect prognosis of gastric cancer patients, the methylation level of Ndrg2 might serve as an independent marker to predict the DFS of the patients.

Bottom Line: 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.We found that H. pylori silenced Ndrg2 by activating the NF-κB pathway and up-regulating DNMT3b, promoting gastric cancer progression.

View Article: PubMed Central - PubMed

Affiliation: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, Hangzhou, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus