Research Of The Relationship Between The Expression Of ZNF139mRNA And The Methylation Of Runx3in Gastric Carcinoma

Objective: Gastric cancer is the common malignant tumor which couldoccurred in any parts of the stomach, having a high morbidity and mortality.China has a huge number of gastric cancer patients.There are more than1million new cases of gastric cancer in global each year, China accounted for42%of them, and almost800000people die of gastric cancer each year, Chinaaccounted for35%. China is one of the countries which have the highestincidence and mortality of gastric cancer, and the incidence and mortality isover twice as much as the world’s average. There are almost400000newcases of gastric cancer in our country every year, that is to say, one Chinesewill die of gastric cancer on each three minutes on average. Even in theleading domestic hospital, the patients’5years of survival rate is onlyforty-six point percent, which is lower than the international advanced level.Therefore, researching the occurrence, development and prognosis of gastriccancer is extremely important. The tumor， in essence， is genetic disease.Various environmental and genetic carcinogenic factors cause DNA damagedsynergistically or sequentially, then activate and （or） and inactivate tumorsuppressor genes, with apoptosis-regulated genes and （or） DNA-repaired genechanging, the expression level of the gene Become abnormal, leading to thetarget cells transformed. The transformed cells firstly have a polyclonalhyperplasia, after a long multistage evolution, one of the clone unlimitedamplify relatively, form the subclone that has diffrrent characteristicsselectively by attaching mutation （heterogeneity）, so as to obtain the ability ofinvasion and metastasis （malignant transformation）, then form malignanttumor. Zinc finger protein is the protein which has the short and stablestructure that combined with Zn²⁺and can fold itself into "fingers" shape. Because of its structural characteristics, Zinc finger protein can bind specifictarget structure selectively, making zinc finger protein play an important rolein the regulation of gene expression, cell differentiation, embryonicdevelopment and orther life processes. The Krüppel-type ZNF gene family isone of the largest gene families of zinc finger transcriptional factors in thehuman genome. Studies have indicated that the members of the KRAB-ZNFfamily can regulate the transcription and translation of relative genes andthen are involved in tumorigenesis and multidrug resistance oftumors.ZNF139gene belongs to the Krüppel-type ZNF gene family, in thepresent there is less study on the role of ZNF139gene in tumorigenesis andmultidrug resistance of gastric carcinoma. As one of the human runt-relatedtranscription factors, the RUNX3gene is found to be an anti-oncogene. Itplays an important role in the TGF-βsignaling pathway. The mechanism ofRUNX3inactivation involves loss of heterozygosity （LOH） and promoterhypermethylation, resulting in the development and metastasis of gastriccancer. In this study, RT-PCR and MSP were performed to evaluate themRNA expression of ZNF139and the methylation of Runx3in55cases ofgastric carcinoma and normal gastric mucosa and lymph （different gender, age,tumor size, organization credits type, infiltration depth, lymph node metastasisand clinical staging）, to investigate the correlation between the mRNAexpression of ZNF139and the methylation of Runx3, the relationship betweenclinicopathological parameters and the correlation was also analysed todiscusses the role ZNF139play in the occurrence evolution in gastric cancer.Methods: The specimens of55cases with gastric carcinoma and relevantnormal gastric mucosa were collected. RT-PCR and MSP were performed inthese tissues for the expressions of ZNF139mRNA and the methylation ofRunx3. Analyzing the relationship between the expressions of ZNF139mRNAand the methylation of Runx3. The results were analyzed with patients’clinicopathological parameters. SPSS19.0software was adopted to carry outthe data processing and analyses, and significance was assessed in allexperiments as a probability value of P<0.05. Results:1. ZNF139mRNA expression level in gastric carcinoma and normalgastric mucosa, and the relationship between the patients’ clinicopathologicalparameters and the level:The expression of ZNF139mRNA in gastric carcinoma was significantlyhigher than that in normal gastric mucosa,（0.6592±0.2291VS0.3540±0.0836）, the difference was statistically significant （t=9.281, P=0.000<0.05）. The expression level of ZNF139mRNA in gastric carcinoma wasclosely related to the tumor size, differentiation degree, infiltration depth andlymph node metastasis（P <0.05）, but not related to the patients’ age andgender （P≥0.05）.2. Runx3methylation status in gastric carcinoma and normal gastricmucosa, and the relationship between the patients’ clinicopathologicalparameters and the status:The methylation rate of Runx3in gastric carcinoma and normal gastricmucosa were54.55%（30/55） and7.27%（4/55）, the difference wasstatistically significant （chi-square=28.778, P=0.000<0.05）. Themethylation level of Runx3in gastric carcinoma was related to the tumordifferentiation degree, infiltration depth and lymph node metastasis （P <0.05）,but not renlated to the patients’ tumor size, age and gender （P≥0.05）.3. The correlation between the expression of ZNF139mRNA and themethylation level of RUNX3in gastric carcinoma, and the relationshipbetween the patients’ clinicopathological parameters and the correlation:The expression level of ZNF139mRNA of the gastric carcinoma whoseRunx3gene methylation happened was obviously higher than the ones whoseRunx3gene Unmethylated （0.8030±0.1952and0.4866±0.1231）, thedifference was statistically significant （t=7.017, P=0.000<0.05）.Statistics analysis indicated that, Runx3gene methylation status andZNF139mRNA expression level in gastric carcinoma is highly consistentpositive correlation （ZNF139mRNA≥0.6was high expression,ZNF139mRNA <0.6was low expression, McNemar Test=1.000≥0.05, Kappa=0.707）. The consistency that Runx3gene methylation andZNF139mRNA high expression was not related to the patients’ gender, ageand tumor size （P≥0.05）, but related to tumor differentiation degree,infiltration depth and lymph node metastasis situation about （P <0.05）.Conclusion:1. The expression of ZNF139mRNA in gastric carcinoma wassignificantly higher than that in normal gastric mucosa, the expression levelhad nothing to do with the patients’ gender and age, but was negativelycorrelated with the differentiation of tumor cells and positively correlated withthe tumor size, infiltration depth,lymph node metastasis, indicating that theZNF139may be related to the occurrence of gastric cancer, and participate inthe evolution process of gastric cancer, affectting the prognosis of the patients.2. The methylation rate of Runx3in gastric carcinoma was obviouslyhigher than that in normal gastric mucous. The methylation level wasnegatively correlated with tumor differentiation, but positively correlated withtumor infiltration depth and lymph node metastasis. It is not related to thetumor size, patients’ age and gender, which indicated that Runx3genemethylation maybe play a promoting role in the occurrence and developmentof gastric cancer.3. The expression level of ZNF139mRNA of the gastric carcinomawhose Runx3gene methylation happened was obviously higher than the oneswhose Runx3gene unmethylated. The methylation status of Runx3gene andthe expression level of ZNF139mRNA has a highly positively consistentcorrelation, and the positive correlation was not related to the patients’ gender,age and tumor size,while related to the differentiation of tumor, infiltrationdepth and lymph node metastasis, indicated that Runx3may have the synergyto participate in the occurrence, development, invasion and metastasis ofgastric cancer by rasing the expression level of ZNF139mRNA.