胃癌组织ZNF139与RUNX3基因甲基化相关性及其生物学意义探讨

Relationship between ZNF139 mRNA and methylation of RUNX3 in gastric cancer and the investigation of the biology behavior

目的:检测胃癌组织中钙指蛋白139(znic finger protein 139,ZNF139)基因的表达和RUNX3基因的甲基化状态,探讨两者之间的相关关系及其生物学意义。方法:对55例胃癌组织及相应的癌旁组织采用逆转录-聚合酶链反应(RT-PCR)检测ZNF139mRNA的表达情况,甲基化特异性PCR技术检测RUNX3基因的甲基化状态,分析两者之间的相关性。结果:ZNF139在胃癌组织中表达(0.659 2±0.229 1)明显高于癌旁组织(0.354 0±0.083 6),t=9.281,P<0.001;胃癌组织ZNF139表达与肿瘤大小有关,t=2.453,P=0.017;与分化程度有关,t=5.162,P<0.001;与浸润深度有关,t=4.145,P<0.001;与淋巴结转移有关,t=4.279,P<0.001。胃癌组织Runx3甲基化率为54.55%,明显高于癌旁组织(7.27%),χ2=28.778,P<0.001;胃癌组织Runx3基因的甲基化水平与肿瘤分化程度有关,χ2=3.911,P=0.048;与浸润深度有关,χ2=7.333,P=0.007;与淋巴结转移有关,χ2=10.530,P=0.001。发生Runx3基因甲基化的胃癌组织ZNF139表达强度(0.803 0±0.195 2)明显高于未发生Runx3甲基化的为胃癌组织(0.486 6±0.123 1),t=7.017,P<0.001,胃癌组织中Runx3基因的甲基化状态和ZNF139的表达强度呈明显正相关性,t=1.000,Kappa=0.707。结论:胃癌组织中存在ZNF139表达上调及Runx3基因甲基化率增高现象,且两者存在高度相关的一致性,提示ZNF139表达上调及Runx3基因甲基化可能通过协同作用参与了胃癌的进展及转移。

OBJECTIVE： To investigate the expression of znic finger protein 139 （ZNF139） and methylation of RUNX3 in gastric cancer and their relationship with clinicopathological characteristics. METHODS： Fifty-five cases of gastric fresh tumor specimens and paired tumor-adjacent tissues were collected. Expressions of ZNF139 were determined by RT-PCR,and methylation of RUNX3 was tested by methylation-specific PCR （MSP） assay to analyse the relationship be tween the expressions of ZNF139 mRNA and the methylation of Runx3. The data of clinicopathological characteristics were also recorded to investigate the biology behavior. RESULTS： Expressions of ZNF139 was stronger in tumors （0.659 2±0. 229 1） than that in tumor-adjacent tissues （0. 354 0±0.083 6）,t=9. 281,P〈0.001. Overexpression of ZNF139 was correlated with tumor size, differentiation, tumor invasion depth, lymph node metastasis （t were 2. 453, 5. 162,4. ]45,4. 279 respectively,P=0. 017,〈0. 001,〈0. 001,〈0. 001）. Rate of RUNX3 methylation in gastric cancer （54.55%） was higher than that in tumor-adjacent tissues （7.27% ,x2 =28. 778,P〈0. 001）. Rate of RUNX3 methylation was correlated with differentiation,tumor invasion depth, lymph node metastasis （7.2 were 3. 911,7. 333,10. 530 respec tively, P were 0.04：8,0. 007,0. 001）. The expression level of ZNF139 mRNA of the gastric carcinoma in which Runx3 gene methylation existed（0. 803 0±0. 195 2） was obviously higher than the one in which Runx3 gene was unmethylated （0. 486 6±0. 123 1）, t= 7. 017, P〈0. 001. Significant relationship was found between ZNF139 mRNA and methylation of RUNX3 （t=l. 000, Kappa= 0. 707）. CONCLUSIONS： ZNF139 is overexpressed in gastric cancer, and rate of RUNX3 methylation is up-regulated. They may be involved in progression and metastasis of gastric cancer.