Methylated cyclin D2 gene circulating in the blood as a prognosis predictor of hepatocellular carcinoma.
Methylated cyclin D2 gene circulating in the blood as a prognosis predictor of hepatocellular carcinoma.
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DOI：
10.1016/j.cca.2010.01.004
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发表时间：
2010-04
期刊：
影响因子：
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通讯作者：
M. Tsutsui;N. Iizuka;T. Moribe;T. Miura;Naoki Kimura;S. Tamatsukuri;H. Ishitsuka;Y. Fujita;Y. H
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文献类型：
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作者：
M. Tsutsui;N. Iizuka;T. Moribe;T. Miura;Naoki Kimura;S. Tamatsukuri;H. Ishitsuka;Y. Fujita;Y. H
背景肝细胞癌（HCC）的复发率高，预后差.方法采用实时荧光定量RT-PCR和甲基化特异性定量PCR方法检测肝癌患者血清中CCND 2基因甲基化水平及其mRNA水平，并与肝切除术后早期肝内复发（IHR）患者进行比较。我们还发现，这种下调是由于启动子高甲基化。在70例接受根治性肝切除术的HCC患者中，39例血清甲基化CCND 2基因阳性（血清> 70 pg/ml）患者的无病生存期（DFS）显著短于31例血清甲基化CCND 2基因阴性患者（P=0.02）。没有血清阴性患者表现出早期IHR，这种血清检测方法没有产生任何早期IHR的假阴性预测。多因素分析显示，血清CCND 2甲基化水平是DFS的独立危险因素（hazardratio为1.866，95%CI：1.106-3.149）。
BACKGROUNDPrognosis of hepatocellular carcinoma (HCC) remains poor because of high recurrence rate. We examined preoperatively the methylated CCND2 gene levels present in the serum following release from HCC cells as a prognosis predictor in patients undergoing curative hepatectomy.METHODSQuantitative real-time RT-PCR and quantitative methylation-specific PCR were used to measure methylated CCND2 gene and its mRNA levels.RESULTSThe CCND2 mRNA levels were down-regulated in HCC with early intrahepatic recurrence (IHR) within 1year of curative hepatectomy. We also identified that this down-regulation was due to promoter hypermethylation. In 70 HCC patients who underwent curative hepatectomy, 39 patients sero-positive for the methylated CCND2 gene (>70pg/ml serum) exhibited a significantly shorter disease-free survival (DFS) period (P=0.02) than the 31 patients who were sero-negative for the methylated CCND2 gene. None of the sero-negative patients demonstrated early IHR, and this method of serum testing did not produce any false-negative predictions for early IHR. Multivariate analysis showed that the serum level of methylated CCND2 was an independent risk factor for DFS (hazard ratio of 1.866, 95% CI: 1.106–3.149).CONCLUSIONMethylated CCND2 gene in the serum serves as a prognosis predictor of HCC after curative hepatectomy.