Abstract:
BACKGROUND:Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In the present study, we investigated the global gene expression associated with stomach carcinogenesis and prognosis of human gastric cancer using a mouse model. METHODS:To find candidate genes involved in stomach carcinogenesis, we firstly constructed a carcinogen-induced mouse gastric tumor model combined with H. pylori infection and high-salt diet. C57BL/6J mice were given N-methyl-N-nitrosourea in their drinking water and sacrificed after 40 weeks. Animals of a combination group were inoculated with H. pylori and fed a high-salt diet. Gene expression profiles in glandular stomach of the mice were investigated by oligonucleotide microarray. Second, we examined an availability of the candidate gene as prognostic factor for human patients. Immunohistochemical analysis of CD177, one of the up-regulated genes, was performed in human advanced gastric cancer specimens to evaluate the association with prognosis. RESULTS:The multiplicity of gastric tumor in carcinogen-treated mice was significantly increased by combination of H. pylori infection and high-salt diet. In the microarray analysis, 35 and 31 more than two-fold up-regulated and down-regulated genes, respectively, were detected in the H. pylori-infection and high-salt diet combined group compared with the other groups. Quantitative RT-PCR confirmed significant over-expression of two candidate genes including Cd177 and Reg3g. On immunohistochemical analysis of CD177 in human advanced gastric cancer specimens, over-expression was evident in 33 (60.0%) of 55 cases, significantly correlating with a favorable prognosis (P = 0.0294). Multivariate analysis including clinicopathological factors as covariates revealed high expression of CD177 to be an independent prognostic factor for overall survival. CONCLUSIONS:These results suggest that our mouse model combined with H. pylori infection and high-salt diet is useful for gene expression profiling in gastric carcinogenesis, providing evidence that CD177 is a novel prognostic factor for stomach cancer. This is the first report showing a prognostic correlation between CD177 expression and solid tumor behavior.
journal_name
BMC Gastroenteroljournal_title
BMC gastroenterologyauthors
Toyoda T,Tsukamoto T,Yamamoto M,Ban H,Saito N,Takasu S,Shi L,Saito A,Ito S,Yamamura Y,Nishikawa A,Ogawa K,Tanaka T,Tatematsu Mdoi
10.1186/1471-230X-13-122subject
Has Abstractpub_date
2013-07-30 00:00:00pages
122issn
1471-230Xpii
1471-230X-13-122journal_volume
13pub_type
杂志文章abstract:BACKGROUND:The mortality due to hemorrhage of esophageal varices (EV) is still high. The predominant cause for EV is liver cirrhosis, which has a high prevalence in Western Europe. Therefore, non-invasive screening markers for the presence of EV are of interest. Here, we aim to investigate whether non-inflammatory gall...
journal_title:BMC gastroenterology
pub_type: 杂志文章
doi:10.1186/s12876-018-0852-5
更新日期:2018-08-02 00:00:00
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pub_type: 杂志文章
doi:10.1186/s12876-015-0324-0
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2010-08-23 00:00:00
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journal_title:BMC gastroenterology
pub_type: 杂志文章,meta分析,评审
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pub_type: 杂志文章,meta分析
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pub_type: 杂志文章,多中心研究,随机对照试验
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pub_type: 杂志文章,meta分析
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journal_title:BMC gastroenterology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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