【摘要】 目的:在外周血游离DNA中筛选肝癌特异的甲基化谱。方法:收集55例肝癌和54例慢性肝病患者血浆标本,应用甲基化特异性PCR方法检测血浆游离DNA的12个抑癌基因甲基化状态。结果:在肝癌组中,APC、p16、GSTP1、Cyclin D2、LHX1、TFPI2、DKK2、DKK3、SFRP2、14-3-3 sigma、ppENK、NPTX2基因的甲基化频率分别为78.18%、63.64%、58.18%、49.09%、49.09%、47.27%、40.00%、18.18%、16.36%、9.09%、7.27%和5.45%,而在慢性肝病组中,各基因的甲基化频率分别为27.78%、22.22%、7.41%、3.70%、16.67%、37.04%、37.04%、11.11%、20.37%、7.41%、7.41%和9.26%。APC、Cyclin D2、TFPI2、DKK3和GSTP1基因在肝癌组中的甲基化频率高于慢性肝病组(P<0.01)。将它们组成5基因甲基化谱,肝癌组甲基化指数(中位值为0.6,IQR 0.4~0.8)显著高于慢性肝病组(中位值为0.2,IQR 0~0.2)。在肝癌组中,甲基化指数与患者年龄具有相关性,年龄大者甲基化指数较高,而甲基化指数与其它临床病理参数未见相关性。甲基化指数与肝癌患者的无瘤生存期及总体生存期均未见相关性。结论:该甲基化谱可能成为肝癌辅助诊断的核酸标志物。更多还原

【Abstract】 Objective: This study aimed to detect the special methylation profile in peripheral blood for hepatocellular carcinoma(HCC). Methods: The methylation status of 12 tumor suppressor genes(TSGs) in the plasma of 55 HCCs and 54 chronic liver diseases(CLDs) was tested by methylation-specific PCR(MSP). Results: In HCC, the methylation frequencies were 78.18% in APC, 63.64% in cyclin D2, 58.18% in TFPI2, 49.09% in DKK3, 49.09% in GSTP1, 47.27% in p16, 40.00% in Sigma 14-3-3, 18.18% in SFRP2, 16.36% in ppENK, 9.09% in DKK2, 7.27% in NPTX2, and 5.45% in LHX1. In CLD, the methylation frequencies were 27.78% in APC, 22.22% in cyclin D2, 7.41% in TFPI2, 3.70% in DKK3, 16.67% in GSTP1, 37.04% in p16, 37.04% in Sigma 14-3-3, 11.11% in SFRP2, 20.37% in ppENK, 7.41% in DKK2, 7.41% in NPTX2, and 9.26% in LHX1. The methylation frequencies of APC, cyclin D2, TFPI2, DKK3, and GSTP1 were higher in HCC than in CLD(P<0.01). The methylation index(MI) of the five-gene methylation profile was statistically higher in HCC(median, 0.6; IQR, 0.4-0.8) than CLD(median, 0.2; IQR, 0-0.2)(P<0.01). In HCC, MI was statistically related to the patient’s age. Older patients with HCC had a higher MI. No significant correlation was observed between MI and other clinicopathological data. Moreover, MI was not related to the disease free survival and the overall survival in HCC. Conclusion: This five-gene methylation profile may be a promising biomarker for the assistant diagnosis of HCC.更多还原