外周血P16、E-cad和hMLH1基因启动子甲基化在胃癌早期诊断中的价值

Value of P16、E-cad and hMLH1 Gene Promoter Methylation in Early Detection of Gastric Carcinoma

目的探讨外周血中P16、E-cad和hMLH1基因启动子甲基化在胃癌早期诊断中的价值。方法收集83例早期胃癌和37例癌前病变及20例健康人群的血浆,提取血浆标本的DNA,采用甲基化特异性PCR(MSP),检测血浆标本中P16、E-cad和hMLH1基因启动子甲基化状态,分析外周血标本中P16、E-cad和hMLH1基因启动子甲基化与其临床病理的关系。结果胃癌外周血标本中P16、E-cad和h MLH1基因启动子甲基化率分别为51.81%、46.99%和43.37%;胃癌前病变外周血组分别为37.84%、29.72%和29.72%;正常对照组分别为0、0和5%。P16、E-cad和hMLH1三个基因联合检测时胃癌与癌前病变组甲基化率分别为77.11%和56.76%。P16、E-cad和hMLH1基因启动子甲基化状态与早期胃癌患者的性别、年龄、肿瘤大小、淋巴结转移及TNM分期无关(P>0.05)。结论 P16、E-cad和hMLH1基因启动子甲基化水平在早期胃癌外周血中升高,通过联合检测患者P16、E-cad和hMLH1基因启动子甲基化有可能成为胃癌早期诊断的指标。

Objective To detect the value of P16、E-cad and hMLH1 gene promoter methylation in early detection of gastric carcinoma（ GC） .Methods 83 patients with GC,37 patients with precancerous lesion and 20 normal controls were col-lected.The methylation statuses of P16、E-cad and hMLH1 in these plasma samples were determined using methylation specific PCR method.Results The methylation rates of P16、E-cad and hMLH1 in GC plasma were 51.81%、46.99%and 43.37%,re-spectively,which were significantly higher than those in plasma from patients with precancerous lesion （37.84%、29.72% and 29.72%,P〈0.05） and normal controls （0、0 and 0,P〈0.05）.Methylation rates of the combination analysis of P16、E-cad and hMLH1 in patients with GC and precancerous lesion were 77.11%、56.76%,respectively.No significant associations existed be-tween the methylation status of the 3 genes and clinical characteristics included sex,age,tumor diameter,lymph node metastases, and TNM stage（P〉0.05）.Conclusion DNA methylation level of P16、E-cad and hMLH1 of plasma are significantly higher in GC patients than patients with precancerous lesion.The combination analysis of P16、E-cad and hMLH1 of the plasma DNA meth-ylation can be indicator for early diagnosis of GC.