摘要
背景与目的:有研究报道基因启动子区CpG岛甲基化引起的钙粘蛋白(E-cadherin,E-cad)基因失活可能在胃癌的发生发展中起重要作用。本研究拟通过检测胃癌组织、癌前病变组织和正常对照组织中E-cad基因启动子区CpG岛甲基化水平及其表达,结合临床病理资料,分析其与胃癌发生、发展的关系。方法:用甲基化特异性聚合酶链反应(methylation-specific PCR,MSP)检测41例胃癌组织、40例癌前病变组织和38例正常对照组织中E-cad基因启动子5′CpG岛甲基化,将PCR扩增产物克隆并测序。应用免疫组化检测基因的蛋白表达。结果:胃癌组织中E-cad基因甲基化阳性率为19.5%(8/41),癌前病变组织为2.5%(1/40),而正常对照组织为0.0%(0/38),前组与后两组之间的差异均有统计学意义(P<0.05)。胃癌组织中E-cad蛋白阳性率为70.7%(29/41),癌前病变组织为97.5%(39/40),正常对照组织为100.0%(38/38),前组与后两组之间的差异均有统计学意义(P<0.05)。低分化型胃癌组织的E-cad基因甲基化阳性率明显高于高分化型(43.8%vs.4.0%)(P<0.05)。有淋巴结转移的胃癌组织中E-cad基因甲基化阳性率与无转移组的差异有统计学意义(33.3%vs.5.0%)(P<0.05)。浸润深达浆膜层的胃癌组织中甲基化阳性率与未达浆膜层组的差异有统计学意义(35.0%vs.4.8%)(P<0.05)。胃癌组织中,E-cad基因甲基化阳性组的蛋白阳性率显著低于甲基化阴性组(0.0%vs.87.9%)(P<0.05)。结论:胃癌组织中存在E-cad基因启动子5′CpG岛高甲基化;从胃癌前病变、低度恶性到高度恶性的胃癌,E-cad基因的高甲基化水平呈不断增加的趋势。
BACKGROUND ＆ OBJECTIVE： CpG island hypermethylation in promoter region of E-cadherin （E-cad） gene plays an important role in tumorigenesis of many tumors. This study was to explore the correlation of E-cadherin hypermethylation to tumorigenesis and development of gastric cancer. METHODS.. Methylation-specific polymerase chain reaction （MSP） was used to detect the methylation of E-cad gene in 41 specimens of gastric cancer, 40 specimens of premalignant gastric lesions and 38 specimens of normal gastric tissues. The expression of E-cad protein was detected by SP immunohistochemistry. RESULTS： The positive rate of E-cad gene methylation was significantly higher in gastric cancer than in premalignant lesions and normal tissues （19.5% vs. 2.5% and 0.0%, P〈0.05）. The positive rate of E-cad protein was significantly lower in gastric cancer tissues than in premalignant lesions and normal tissues （70.7% vs. 97.5% and 100.0%, P〈0.05）. The positive rate of E-cad gene methylation was significantly higher in poorly differentiated cancer tissues than in well differentiated cancer tissues （43.8% vs. 4.0%, P〈0.05）, significantly higher in gastric cancer tissues with lymph node metastasis than in those without lymph node metastasis （33.3% vs. 5.0%, P〈0.05）, and significantly higher in gastric cancer tissues with serosa invasion than in those without serosa invasion （35.0% vs. 4.8%, P〈0.05）. The positive rate of E-cad protein was significantly lower in gastric cancer tissues with E-cad gene methylation than in those without E-cad gene methylation （0.0% vs. 87.9%, P〈0.05）. CONCLUSION： CpG island hypermethylation of E-cad gene exists in gastric cancer, which down-regulates E-cad expression and might be involved in tumorigenesis and development of gastric cancer.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2007年第11期1199-1203,共5页
Chinese Journal of Cancer
基金
天津医科大学科研基金(No.2003ky55)~~
