Methylation Status of MGMT Gene Promoter in Patients with Adenocarcinoma of Esophagogastric Junction and Its Relationship with Prognosis
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摘要:目的
检测食管胃交界部腺癌组织中O6-甲基鸟嘌呤-DNA甲基转移酶（O6-methylguanine-DNA methyltransferase, MGMT）基因启动子区甲基化状态以及蛋白表达情况，评价其与临床参数及预后的关系。
方法选取107例食管胃交界部腺癌患者，应用甲基化特异性聚合酶链反应（methylmion specific PCR, MSP）检测MGMT基因甲基化情况，免疫组织化学法检测MGMT蛋白表达情况，分析两者与临床特征及生存时间的关系。
结果癌组织中MGMT基因启动子区甲基化率显著高于癌旁正常组织；癌组织中MGMT蛋白阳性率显著低于癌旁正常组织。Spearman等级相关分析表明MGMT基因启动子区甲基化与MGMT蛋白表达呈负相关。MGMT基因启动子甲基化及蛋白表达与淋巴结转移、pTNM分期之间具有相关性。多因素Cox回归分析，MGMT基因启动子区甲基化、MGMT蛋白表达及pTNM分期是影响患者生存的独立预后因素。
结论MGMT基因启动子甲基化、MGMT蛋白表达与pTNM分期是影响食管胃交界部腺癌患者预后的独立影响因素。
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关键词:
- 食管胃交界部腺癌 /
- MGMT基因 /
- 甲基化特异性聚合酶链反应 /
- 免疫组织化学
Abstract:ObjectiveTo detect the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter and its protein expression in adenocarcinoma of esophagogastric junction (AEJ) tissues. The relationship of MGMT methylation status and its protein expression with clinical features and survival were also analyzed.
MethodsThe methylation status of MGMT promoter was detected by methylation specific polymerase chain reaction (MSP) in 107 AEJ cases. Immunohistochemistry staining was used to detect protein expression in the same group of specimen. Then, the relationship of MGMT methylation with clinical features and prognosis were analyzed.
ResultsThe promoter methylation rate of MGMT in cancerous specimen was higher than that in adjacent normal group. However, the MGMT expression rate was opposite. A correlation between promoter methylation of MGMT and protein expression were established by Spearman correlation analysis. MGMT promoter methylation and its protein expression had significant correlation with lymph node metastasis and pTNM stage. The Cox multivariate regression analysis indicated that MGMT promoter methylation, MGMT protein expression and pTNM stage were significant risk factors.
ConclusionThe promoter methylation of MGMT, MGMT protein expression and pTNM stage might be significant influence factors for 5 years survival time of AEJ patients.
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图 1 食管胃交界部腺癌组织中MGMT启动子甲基化
Figure 1 Methylation status of MGMT promoter in adenocarcinoma of esophagogastric junction
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图 2 食管胃交界部腺癌组织中MGMT蛋白表达 (SP×400)
Figure 2 The expression of MGMT protein in adenocar cinoma of esophagogastric junction tissues (SP×400)
表 1 MGMT基因启动子区甲基化和MGMT蛋白表达与临床特征的相关性
Table 1 Relationship of MGMT methylation and its expression with clinical features
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表 2 MGMT引物序列、产物大小及退火温度
Table 2 Primer sequence, product size and annealing temperature of MGMT
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表 3 MGMT基因启动子区甲基化状态与MGMT蛋白表达的相关性 (n)
Table 3 Correlation between promoter methylation of MGMT and MGMT protein expression (n)
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表 4 影响食管胃交界部腺癌术后患者预后的相关分析
Table 4 Prognosis-related factors in patients with adenocarcinoma of esophagogastric junction
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