贲门腺癌Wif-1基因启动子区甲基化状态的检测及临床意义  

Detection and clinical significance of Wif-1 promoter methylation in gastric cardiac adenocarcinoma: report of 94 cases

作　　者：郭艳丽[1] 郭炜[1] 靳国梁 杨植彬[1] 邝钢[1] 孙萍萍[3] 董稚明[1] 

机构地区：[1]河北医科大学第四医院肿瘤研究所病理室,石家庄050011 [2]河北省磁县肿瘤医院病理室,河北邯郸056000 [3]北京市怀柔区第一医院病理科,北京101400

出　　处：《第三军医大学学报》2009年第21期2094-2097,共4页Journal of Third Military Medical University

基　　金：河北省强势特色学科基金(2005-52);河北省科技厅科技攻关项目(052761163)~~

摘　　要：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 promoter methylation of Wif-1 in gastric cardiac adenocarcinoma （ GCA） . Methods Tumor samples of 94 cases of GCA before chemotherapy and radiotherapy admitted in our hospital from January 2004 to December 2006 were collected,and their normal mucosal tissues served as normal control. Nested methylation-specific PCR （ MSP） and RT-PCR were applied respectively to examine the Wif-1 promoter methylation and its mRNA expression in tumors and corresponding normal mucosal tissues. Immunohistochemical staining was used to determine the protein expression of β-catenin. The correlation of the Wif-1 methylation and clinical data was analyzed. Results The frequency of Wif-1 promoter methylation in GCA and corresponding normal mucosa were 61. 7% （ 58 /94） and 34. 0% （ 32 /94） ,respectively. The frequency of Wif-1 promoter methylation in GCA was significantly higher than that in normal mucosa （ χ^2 = 14. 409,P = 0. 000） . In the tissues of GCA and normal mucosa,the positive rate of Wif-1 mRNA expression were 10. 6% （ 10/94） and 86. 2% （ 81/94） ,and the protein expression of β-catenin were 90. 4% （ 85/94） and 38. 3% （ 36/94） . The expression of Wif-1 mRNA and β-catenin protein were correlated with the frequency of Wif-1 methylation in the GCA tissues （ P〈0. 01） . Furthermore,the frequency of Wif-1 methylation was correlated with the invasion depth and lymphatic metastasis （ P〈0. 05） ,but not with pathological classification and clinical stage. Conclusion CpG methylation of the Wif-1 promoter is a frequent event in GCA and may contribute to pathogenesis of GCA through aberrant canonical Wnt/ β-catenin signaling pathway.

关 键 词：贲门腺癌 甲基化 WIF-1基因 Β-CATENIN 

分 类 号：R394.3[医药卫生—医学遗传学] R730.23[医药卫生—基础医学]