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目的研究贲门腺癌(gastric cardiacadenoc arcinoma,GCA)中Wnt抑制因子-1(Wntinhibitory factor-1,Wif-1)基因启动子区甲基化状态及表达情况,探讨其与贲门癌发生的关系及可能机制。方法分别用巢式甲基化特异性PCR(MSP)和RT-PCR方法检测贲门腺癌及相应正常黏膜组织中Wif-1基因的甲基化状态和mRNA表达水平;应用免疫组化S-P法检测β-catenin蛋白的表达情况。结果Wif-1基因在贲门腺癌及正常黏膜组织中的甲基化率分别61.7%(58/94)和34.0%(32/94),癌组织中Wif-1基因的甲基化率明显高于正常黏膜组织(χ2=14.409,P=0.000);癌及正常黏膜组织中Wif-1基因mRNA的阳性表达率分别为10.6%(10/94)和86.2%(81/94),β-catenin蛋白的异质表达率分别为90.4%(85/94)和38.3%(36/94),癌组织中Wif-1mRNA表达及β-catenin蛋白的表达均与Wif-1基因的甲基化明显相关(P<0.01);Wif-1基因的甲基化与肿瘤的浸润深度及淋巴结转移相关(P<0.05),而与肿瘤的病理分级及临床分期无关。结论Wif-1基因启动子区甲基化在贲门腺癌中频繁发生,可能通过引起经典Wnt/β-catenin通路的异常激活与贲门腺癌的发生密切相关。
Objective To investigate the methylation status and expression of Wnt inhibitor of metalloproteinases-1 (Wif-1) gene in gastric cardiac adenocarcinoma (GCA) and to investigate its possible relationship with cardia carcinoma mechanism. Methods The methylation status and mRNA expression of Wif-1 gene in gastric cardia adenocarcinoma and its corresponding normal mucosa tissues were detected by nested methylation-specific PCR (MSP) and RT-PCR, respectively. The expression of Wif- β-catenin protein expression. Results The methylation rates of Wif-1 gene in gastric cardia adenocarcinoma and normal mucosa tissues were 61.7% (58/94) and 34.0% (32/94), respectively. The methylation rate of Wif-1 gene was significantly higher in cancer tissues The positive rates of Wif-1 mRNA in normal mucosa (χ2 = 14.409, P = 0.000) were 10.6% (10/94) and 86.2% (81/94) in normal mucosa, The expression of Wif-1mRNA and β-catenin protein were significantly correlated with the methylation of Wif-1 gene in cancerous tissues (90.4% (85/94) and 38.3% (36/94), respectively) (P <0.01). The methylation of Wif-1 gene was correlated with the depth of tumor invasion and lymph node metastasis (P <0.05), but not with the pathological grade and clinical stage of tumor. Conclusion The methylation of Wif-1 gene promoter in adenocarcinoma of the cardia occurs frequently, which may be closely related to the occurrence of gastric cardia adenocarcinoma by inducing abnormal activation of the canonical Wnt / β-catenin pathway.