TY - JOUR
T1 - Gene expression analysis of a Helicobacter pylori-infected and high-salt diet-treated mouse gastric tumor model
T2 - identification of CD177 as a novel prognostic factor in patients with gastric cancer
AU - Toyoda, Takeshi
AU - Tsukamoto, Tetsuya
AU - Yamamoto, Masami
AU - Ban, Hisayo
AU - Saito, Noriko
AU - Takasu, Shinji
AU - Shi, Liang
AU - Saito, Ayumi
AU - Ito, Seiji
AU - Yamamura, Yoshitaka
AU - Nishikawa, Akiyoshi
AU - Ogawa, Kumiko
AU - Tanaka, Takuji
AU - Tatematsu, Masae
N1 - Funding Information:
This study was supported by Grant-in Aid for the Third-term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare, Japan, Grant-in-Aid for the Cancer Research from the Ministry of Health, Labour and Welfare, Japan, and Grant-in-Aid for Young Scientists B (20790318 and 22700935) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1186/1471-230X-13-122
DO - 10.1186/1471-230X-13-122
M3 - Article
C2 - 23899160
AN - SCOPUS:84880900873
SN - 1471-230X
VL - 13
SP - 122
JO - BMC gastroenterology
JF - BMC gastroenterology
ER -
