O^6-甲基鸟嘌呤-DNA-甲基转移酶基因表达与胃癌发生的关系

Relationship between O^6-Methyguanine DNA-Methyltransferase Gene and Gastric Carcinogenesis

目的研究人胃癌组织O6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)基因的表达特点及其与胃癌发生的关系。方法应用加强型原位杂交方法及寡核苷酸探针高效标记技术对76例胃癌组织、73例癌旁组织、20例正常胃组织进行MGMT基因标记检测,同时应用自动图像分析系统进行定量分析。结果胃癌组织MGMT基因阳性表达率为40.8%(31/76),低于正常胃组织的60.0%(12/20),MGMT表达强阳性率为32.3%(10/31),也明显低于正常组织的83.3%(10/12),差异均有显著性意义(P<0.01或P<0.05);癌旁组织MGMT基因阳性表达率为46.6%(34/73),MG-MT表达强阳性率为41.1%(14/34),与胃癌组织差异无显著性意义。定量分析示,胃癌组织MGMT阳性表达的积分吸光度、阳性单位值明显低于正常组织(P<0.05)。胃癌组织与癌旁组织、早期胃癌与进展期胃癌组织、癌旁不同程度不典型增生之间MGMT表达无明显差异。结论人体胃组织存在高度表达的MGMT基因,胃癌发生与MGMT基因表达水平降低有关,MGMT基因异常表达是胃癌形态学改变出现之前的早期行为。

Objective To study the characteristics. of the expression of O^6-methylguanine-DNA-methyhransferase gene （MGMT） in human gastric carcinoma and its relation with gastric carcinogenesis. Methods The MGMT gene cxpression in 76 cases of gastric carcinomas. 73 cases of prccancerous lesions and 20 gastric normal tissues was detected by means of enhanced sensitive in situ hybridization and highly sensitive digoxygenin-labeled oligonuleolide probe technique. At the same time. quantitative analysis was performed by the automatic image analysis system. Results The positive expression rate of MGMT gene in normal gastric tissues was 60% （12/20）. significantly higher than in gastric carcinomas （40.8%. 31/76. P〈0.05） and precarcerous lesions （46.6% 34/73. P〈0.05）. The strong positive rate of the MGMT expression in gastric normal tissues was 83.3 % （10/12）, significantly higher than in gastric carcinomas （32. 3 %, 10/31, P〈0. 05） and precarcerous lesions （41. 1% . 14/34. P〈0.01）. Automatic image analysis system revealed that the integral optic density CA） and positive units in gastric carcinomas were significantly lower than in normal gastric tissues （P〈0.05）. There was no significant difference in the M MT positive expression between early and progressive gastric carcinomas, precancerous lesions and carcinomas, various stages of dysplasia in precanccrous tissues. Conclusion The MGMT gene expression is present in normal gastric tissues at a high levels. Low MGMT gene expression is closely related to the gastric carcinoma. The abnormal MGMT expression was the early event of gastric carcinoma.