| Objective：Gastric carcinoma is the one of the common malignant tumor,and is leading causes of death in many countries. According to statistics,934,000new cases were found in the world each year, and42%(nearly400,000) were in China. The prevalence and mortality of gastric carcinomaare more than2times in our country than that of the world’s average level, aChinese died of gastric carcinoma in about every2-3minutes. The level ofdiagnosis and treatment has improved in recent years, and the curative ratio ofearly gastric carcinoma can reach more than90%, but the majority of patientsattending doctors is advanced stage, untreated survival rate is less than oneyear. Therefore, early detection and early treatment is the key to reduce gastriccarcinoma mortality. The research of gastric carcinoma occurrence anddevelopment become the mainly discusses direction in recent years. Foundtargeted gene of early gastric carcinoma and prevented in advance is greatsignificance to improve the survival rate.The generation of gastric carcinoma is a complicated process, lots offactors can lead to the occurrence of gastric carcinoma, including DNAmethylation. DNA methylation is an important way of modification whichplays an important role in cell differentiation, embryonic development andcancerous, and closely relate to tumor process and prognosis. A lot ofresearches show that the abnormal activation of Wnt/β-catenin signalingpathways plays an essential role in tumorigenesis. Secreted frizzled relatedprotein (secreted frizzled related proteins, SFRPs) is a kind of family ofsecreted glycoprotein which can directly bind with Wnt antagonist. It locateson chromosome8p12-11.1, coding with the SFRPs gene, and contains300amino acid residue, including a signal sequence, a homologous half cycteine-rich domain (CRD) of N-terminal and a axon guidance protein netrinhydrophilic C-end zone (NTR). SFRPs protein can competitive inhibit thebinding of Frizzled receptor and Wnt ligand, and closed Wnt signalingpathways, prevent cell proliferation. When methylation is happened, the geneexpression is silent, therefore weaken Wnt signaling pathways inhibition,induced its abnormal activation, and promoted tumor occurrence anddevelopment.Helicobacter pylori (Helicobacter pylori, Hp) is already confirmed as theclass I carcinogen of gastric carcinoma. Hp infection leads to gastric mucosadamage, make stomach internal environment change and a series of reaction,which cause gastric carcinoma. The present studies demonstrate that Hpinfection may closely related to some genetic abnormal methylation in gastriccarcinoma and precancerous lesions, and eradicate Hp may reverse DNAmethylation. The further research of the relationship between Hp infection andmethylation mechanism may provide effective risk prediction, and newtherapy for Hp infection patients.Methods:72cases of gastric mucosa samples by electronic gastroscope biopsy,were selected from the fourth hospital of Hebei medical university fromAugust2012to October2012, including15cases of chronic gastritisregarding as the negative control. All cases received no treatment beforebiopsy, exist a complete follow-up material. Genome DNA were usingextracted by the Ezup column type animal genome DNA extraction kit, andthen the methylation of SFRPs gene was detected by methylation specificpolymerase chain reaction (PCR-MSP) in72cases of gastric tissues, whilethe Hp infection status was detected by immunohistochemical Sp method. Allresults were analyzed using SPSS16.0statistical software by χ2test.Results:134cases（47.2%）with methylation of the SFRP1gene promoter CpGisland were found from72cases. Among these34cases,5(33.3%) cases fromsevere dysplasia and and29cases (72.5%) from gastric carcinoma, respectively. The ratio of methylation in dysplasia and gastric carcinomagroup was significantly higher than that in the chronic gastritis group (P<0.05).36cases（48.6%）with methylation of the SFRP2gene promoter CpG islandwere found from72cases. Among the36cases,6(40.0%) cases from severedysplasia tissues and30cases (75.0%) from gastric carcinoma tissues,respectively. The ratio of methylation in severe dysplasia and gastric cancergroup was significantly higher than that in the chronic gastritis group (P<0.05).27cases（37.5%）with methylation of the SFRP4gene promoter CpG islandwere found from72cases. Among the27cases,2(13.3%) cases from severedysplasia tissues and25cases (62.5%) from gastric carcinoma tissues,respectively. The ratio of methylation in severe dysplasia and gastric cancergroup was significantly higher than that in the chronic gastritis group (P<0.05).30cases（41.6%）with methylation of the SFRP5gene promoter CpG islandwere found from72cases. Among the30cases,4cases (26.7%) from severedysplasia and26cases (65.0%) from gastric carcinoma tissues, respectively.The ratio of methylation in severe dysplasia and gastric cancer group wassignificantly higher than that in the chronic gastritis group (P<0.05).2Hp positive rate was30.6%(22/72) in72cases, including5cases ofchronic gastritis,11cases of severe dysplasia and4cases of gastric carcinoma.Hp infection demonstrated significantly higher positive rate in severedysplasia than in chronic gastritis group (P<0.05).3Hp infection were22cases (30.6%) in72cases, while SFRPs gene(SFRP1,2,4,5) methylation positive were34cases (47.2%),36cases(48.6%),27cases (37.5%),30cases (41.6%) respectively, Spearman rankcorrelation analysis showed no relationship between them(r=0.264, P>0.05).Conclusions：1SFRPs genes abnormal methylation is the important factors in theoccurrence and development of gastric carcinoma.2Hp infection is the essential role in the process of gastric carcinomadevelopment, however Hp positive rate decrease in gastric carcinoma. 3Hp infection showed no relationship with SFRPs gene promotermethylation. |
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