Stepwise cumulation of <i>RUNX3</i> methylation mediated by <i>Helicobacter pylori</i> infection contributes to gastric carcinoma progression

Lu, Xiaoxiao; Yu, Jinming; Liu, Ying; Han, Jing; Wang, Shi; Qian, Yu; Wang, Xinbao; Fang, Xian-Hua; Ling, Zhi‐Qiang

doi:10.1002/cncr.27604

Cited by 70 publications

(79 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with previous findings, the present study demonstrated vimentin overexpression in GC cell lines and clinical GC tissues. Over the past decade, knowledge of the importance of epigenetic events in the control of normal cellular processes, and aberrant events leading to tumor development and progression has increased (3)(4)(5)(6)(7)22). DNA methylation is a major epigenetic mechanism that has been intensively investigated in the context of gene regulation and abnormal gene silencing in cancer cells (3)(4)(5)(6).…”

Section: Discussionmentioning

confidence: 99%

“…Gastric tumorigenesis is a complex, multi-step process involving alterations of numerous genes (2). Aberrant promoter methylation is an important mechanism for silencing certain tumor suppressor and tumor-associated genes, and is significant during the pathogenesis and progression of certain types of human cancer (3,4), including GC (5,6). Data suggests that DNA methylation may be a useful biomarker for cancer risk evaluation (3,5), early diagnosis (5), prognosis (4,5) and evaluation of sensitivity to chemotherapy (7).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

DNA hypermethylation of the vimentin gene inversely correlates with vimentin expression in intestinal- and diffuse-type gastric cancer

et al. 2015

View full text Add to dashboard Cite

Abstract. T he vimentin gene is a hallma rk of epithelial-to-mesenchymal transition and has been observed to be overexpressed in various types of tumor cell line and tissue. Previous studies have reported correlations between vimentin DNA methylation levels and subsequent vimentin expression levels in solid tumors, including breast and colorectal cancer; however, to the best of our knowledge, such a correlation has not been reported for gastric cancer (GC) using Lauren classification. Therefore, the present study aimed to quantify DNA methylation levels of the vimentin gene using quantitative (q) methylation-specific polymerase chain reaction (PCR) in intestinal-type GC cell lines (MKN-28, AGS and MKN-1), diffuse-type GC cell lines (SGC-7901, SNU-5 and KATO III), the GES-1 immortalized human non-neoplastic gastric epithelial cell line, as well as in tumor and paratumor normal tissue samples. Furthermore, the present study analyzed the messenger RNA expression of the vimentin gene in these cell lines and tissues by reverse transcription-qPCR. A comparison of the clinicopathological features was conducted between patients, grouped according to the Lauren classification. The present study identified that the vimentin promoter region was hypermethylated in all GC cell lines and tumor tissue samples when compared with immortalized normal gastric epithelial cells and paratumor normal tissues. In addition, vimentin promoter methylation levels were observed to be higher in intestinal-type cell lines when compared with those of diffuse-type lines and tissues. Correspondingly, vimentin expression levels were lower in intestinal-type gastric cell lines compared with those of diffuse-type cell lines and tissues, and were lowest in the non-neoplastic gastric cell line and paratumor normal tissues. Patients with diffuse-type GC were on average younger (P=0.023), and exhibited higher tumor (P=0.020), node (P= 0.032) and TNM classification of malignant tumor stage (P=0.039) than those with intestinal-type GC. Following treatment of AGS cells (which demonstrated the highest methylation level of the vimentin gene) with 5-aza-2'-deoxycytidine, vimentin expression was restored significantly. Thus, the present study revealed that vimentin promoter methylation levels are inversely correlated with vimentin expression levels in GC (according to Lauren classification). High levels of methylation in the vimentin gene promoter region may be involved in carcinogenesis and the development of GC, and may provide a novel molecular classification for GC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNA hypermethylation of the vimentin gene inversely correlates with vimentin expression in intestinal- and diffuse-type gastric cancer

et al. 2015

View full text Add to dashboard Cite

show abstract

“…12 Several studies suggested RUNX-3 methylation as a risk factor for the gastric carcinogenesis in patients with H. pylori infection. 23,24 One study suggested that epigenetic events and gene methylation were not evenly distributed throughout the gastric mucosa, so multiple biopsies in different parts of stomach should be performed to determine methylation status. 8 In this study, one biopsy was used for methylation status, which might be a limitation.…”

Section: 18mentioning

confidence: 99%

Helicobacter pyloriEradication Modulates Aberrant CpG Island Hypermethylation in Gastric Carcinogenesis

Choi

Kim

et al. 2016

Korean J Gastroenterol

View full text Add to dashboard Cite

Background/Aims: Helicobacter pylori infection induces aberrant DNA methylation in gastric mucosa. We evaluated the long-term effect of H. pylori eradication on promotor CpG island hypermethylation in gastric carcinogenesis. Methods: H. pylori-positive patients with gastric adenoma or early gastric cancer who underwent endoscopic resection were enrolled. According to H. pylori eradication after endoscopic resection, the participants were randomly assigned to H. pylori eradication or non-eradication group. H. pylori-negative gastric mucosa from normal participants provided the normal control. CpG island hypermethylation of tumor-related genes (p16, CDH1, and RUNX-3) was evaluated by quantitative MethyLight assay in non-tumorous gastric mucosa. The gene methylation rate and median values of hypermethylation were compared after one year by H. pylori status. Results: In H. pylori-positive patients, hypermethylation of p16 was found in 80.6%, of CDH1 in 80.6%, and of RUNX-3 in 48.4%. This is significantly higher than normal control (p16, 10%; CDH1, 44%; RUNX-3, 16%) (p<0.05). In the H. pylori eradication group, methylation rates of p16 and CDH1 decreased in 58.1% and 61.3% of the patients, and the median values of hypermethylation were significantly lower at one year compared with the non-eradication group. However, RUNX-3 hypermethylation did not differ significantly at one year after H. pylori eradication. The non-eradication group hypermethylation did not change after one year. Conclusions: H. pylori infection was associated with promotor hypermethylation of genes in gastric carcinogenesis, and H. pylori eradication might reverse p16 and CDH1 hypermethylation. (Korean J Gastroenterol 2016;68:253-259)

show abstract

“…A number of studies have showed that RUNX3 promoter region methylation affects its expression and plays an important role in the occurrence of early gastric cancer. Lu et al (2012) analyzed the methylation status of RUNX3 promoters in 220 samples of chronic atrophic gastritis, 196 samples of intestinal metaplasia, 134 samples of gastric adenoma, 102 samples of dysplasia, and 202 samples of gastric cancer with paired noncancerous mucosa tissues and corresponding blood specimens, and found that RUNX3 promoter methylation increased with progression of gastric mucosal lesions: the methylation rates were 15.9% in chronic atrophic gastritis, 36.7% in intestinal metaplasia, 41.8% in gastric adenoma, 54.9% in dysplasia and 75.2% in gastric cancer, indicating that circulating RUNX3 methylation was a valuable biomarker for the detection of early gastric cancer. found that the combined detection of RUNX3 gene methylation and serum CEA, CA19-9 showed higher sensitivity than CEA and CA19-9 combination in the diagnosis of gastric cancer, but no reduced specificity DOI:http://dx.doi.org/10.7314/APJCP.2013.14.6…”

Section: Runt-related Transcription Factor 3 (Runx3)mentioning

confidence: 99%

Serum Protein and Genetic Tumor Markers of Gastric Carcinoma

He¹,

Zhang²

2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

The high incidence of gastric cancer and consequent mortality pose severe threats to human health. Early screening, diagnosis and treatment are the key to improve the prognosis of the patients with gastric cancer. Gastroscopy with biopsy is an efficient method for the diagnosis of early gastric cancer, but the associated discomfort and high cost make it difficult to be a routine method for screening gastric cancer. Serum tumor marker assay is a simple and practical method for detection of gastric cancer, but it is limited by poor sensitivity and specificity. Therefore, people have been looking for novel serum markers of gastric cancer in recent years. Here we review the novel serum tumor markers of gastric cancer and their diagnostic significance, focusing on the discoveries from serum proteomics analyses and epigenetics researches.

show abstract

Stepwise cumulation of RUNX3 methylation mediated by Helicobacter pylori infection contributes to gastric carcinoma progression

Cited by 70 publications

References 45 publications

DNA hypermethylation of the vimentin gene inversely correlates with vimentin expression in intestinal- and diffuse-type gastric cancer

DNA hypermethylation of the vimentin gene inversely correlates with vimentin expression in intestinal- and diffuse-type gastric cancer

Helicobacter pyloriEradication Modulates Aberrant CpG Island Hypermethylation in Gastric Carcinogenesis

Serum Protein and Genetic Tumor Markers of Gastric Carcinoma

Contact Info

Product

Resources

About