Oncology institute, The Fourth Affiliated Hospital of Suzhou University, Wuxi 214062, China.
Exp Mol Pathol. 2011 Aug;91(1):455-60. doi: 10.1016/j.yexmp.2011.05.001. Epub 2011 May 11.
DNA methylation is a promising biomarker for cancer. This study was aimed at investigating the methylation levels of multiple genes in hepatocellular carcinoma (HCC) and to identify a combination of methylation markers that would be useful for the diagnosis of HCC. The methylation status of a panel of nine tumor-associated genes (APC, GSTP1, RASSF1A, CDKN2A, SFRP1, RUNX3, SOCS1, Hint1, and HIC-1) in 8 normal liver tissues and 47 paired HCCs and non-tumorous tissues (NTs) was determined using a modified methylation-sensitive, restriction enzyme-based quantitative PCR (MSRE-qPCR) method. The methylation levels of six genes (APC, CDKN2A, GSTP1, RASSF1A, SFRP1 and RUNX3) were significantly higher in HCCs than in adjacent NTs (P<0.05). Although the AUC (area under the curve) for each individual gene was low to moderate (range: 0.576 to 0.835) according to receiver operator characteristic (ROC) curve analysis, the combination analysis of these six genes resulted in an increase of AUC of 0.954 with 85.1% sensitivity, 89.4% specificity, 88.9% positive predictive value, and 85.7% negative predictive value in discriminating HCC tissues from NT tissues. These results indicate that the analysis of a combination of these six methylated genes may be a promising method for the risk assessment and diagnosis of HCC.
DNA 甲基化是一种很有前途的癌症生物标志物。本研究旨在研究肝癌（HCC）中多个基因的甲基化水平，并确定一组甲基化标志物，这些标志物将有助于 HCC 的诊断。采用改良的甲基化敏感、基于限制性内切酶的定量 PCR（MSRE-qPCR）方法，检测了 8 例正常肝组织和 47 对 HCC 及其相应非肿瘤组织（NT）中 9 个肿瘤相关基因（APC、GSTP1、RASSF1A、CDKN2A、SFRP1、RUNX3、SOCS1、Hint1 和 HIC-1）的甲基化状态。与相邻的 NT 相比，HCC 中 6 个基因（APC、CDKN2A、GSTP1、RASSF1A、SFRP1 和 RUNX3）的甲基化水平显著升高（P<0.05）。虽然根据 ROC 曲线分析，每个基因的 AUC（曲线下面积）较低（范围为 0.576 至 0.835），但对这 6 个基因的联合分析可使 AUC 增加至 0.954，其对 HCC 组织和 NT 组织的鉴别具有 85.1%的敏感性、89.4%的特异性、88.9%的阳性预测值和 85.7%的阴性预测值。这些结果表明，分析这 6 个甲基化基因的组合可能是评估 HCC 风险和诊断 HCC 的一种很有前途的方法。
