Key Laboratory of Artificial Cells, Third Central Hospital, Tianjin 300170, China.
World J Gastroenterol. 2010 Feb 14;16(6):755-63. doi: 10.3748/wjg.v16.i6.755.
To investigate the prevalence and time of Dickkopf (DKK) family methylation and its clinical significance in hepatocarcinogenesis.
Methylation of DKK family genes was quantitatively analyzed in 115 liver tissue samples, including 50 pairs of primary hepatocellular carcinoma (HCC) and matched noncancerous cirrhotic tissue samples, as well as 15 liver cirrhosis biopsy samples.
The methylation level of DKK3 was significantly higher in HCC tissue samples than in matched noncancerous cirrhotic tissue samples (P < 0.0001) or in liver cirrhosis biopsy samples (P = 0.0139). Receiver operator characteristic curve analysis confirmed that the percent of methylated reference (PMR) values of DKK3 could effectively discriminate HCC tissue samples from noncancerous tissue samples (AUC = 0.8146) or liver cirrhosis biopsy samples (AUC = 0.7093). Kaplan-Meier survival curves revealed that the progression-free survival time of patients with a higher DKK3 methylation level (PMR > 1%) was significantly shorter than that of those with a lower DKK3 methylation level (PMR < or = 1%) (P = 0.0255). Multivariate Cox analysis indicated that methylated DKK3 was significantly and independently related with a shorter survival time (relative risk = 2.527, 95% CI: 1.063-6.008, P = 0.036) of HCC patients.
Methylation of DKK3 is an important event in early malignant transformation and HCC progression, and therefore might be a prognostic indicator for risk assessment of HCC.
研究 Dickkopf（DKK）家族甲基化的流行率和时间及其在肝癌发生中的临床意义。
定量分析了 115 例肝组织样本中的 DKK 家族基因甲基化情况，包括 50 对原发性肝细胞癌（HCC）和配对的非癌性肝硬化组织样本，以及 15 例肝硬化活检样本。
HCC 组织样本中 DKK3 的甲基化水平明显高于配对的非癌性肝硬化组织样本（P < 0.0001）或肝硬化活检样本（P = 0.0139）。受试者工作特征曲线分析证实，DKK3 的甲基化参考百分比（PMR）值可以有效区分 HCC 组织样本与非癌组织样本（AUC = 0.8146）或肝硬化活检样本（AUC = 0.7093）。Kaplan-Meier 生存曲线显示，DKK3 甲基化水平较高（PMR > 1%）的患者无进展生存期明显短于 DKK3 甲基化水平较低（PMR < 或 = 1%）的患者（P = 0.0255）。多变量 Cox 分析表明，甲基化 DKK3 与 HCC 患者较短的生存时间显著相关（相对风险 = 2.527，95%CI：1.063-6.008，P = 0.036）。
DKK3 甲基化是早期恶性转化和 HCC 进展的重要事件，因此可能是 HCC 风险评估的预后指标。
