Molecular-based prediction of early recurrence in hepatocellular carcinoma
Molecular-based prediction of early recurrence in hepatocellular carcinoma
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DOI：
10.1016/j.jhep.2004.04.031
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发表时间：
2004-08-01
影响因子：
25.7
通讯作者：
Monden, M
中科院分区：
文献类型：
--
作者：
Kurokawa, Y;Matoba, R;Monden, M
背景/目的：肝细胞癌因肿瘤复发率高，预后极差。由于目前的形态学指标往往不足以用于治疗决策，我们试图确定更多的早期复发的生物学指标。方法：我们使用基于聚合酶链式反应的3072个基因阵列分析了100名肝癌患者的基因表达。通过随机排列试验筛选出预测早期肝内复发的信息基因，构建了加权投票预测方法。结果：通过置换检验，我们筛选出92个基因在复发组和无复发组之间的表达模式存在显著差异。我们的预测方法利用20个排名靠前的基因，正确地预测了验证组内40例患者中29例的早期肝内复发，其优势比为6.8(95%CI1.7-27.5，P=0.010)。征象好和征象差的患者2年复发率分别为29.4%和73.9%。多变量COX分析显示分子标志物是肝癌复发的独立指标(危险比3.82，95%可信区间1.44~10.10，P=0.007)。结论：基于分子标记的20个基因预测方法可用于预测肝癌的早期复发。(C)2004年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background/Aims: Hepatocellular carcinoma (HCC) has a very poor prognosis, due to the high incidence of tumor recurrence. As the current morphological indicators are often insufficient for therapeutic decisions, we sought to identify additional biologic indicators for early recurrence.Methods: We analyzed gene expression using a PCR-based array of 3072 genes in 100 HCC patients. Informative genes predicting early intrahepatic recurrence were selected by random permutation testing, and a weighted voting prediction method was constructed. Following estimation of prediction accuracy, a multivariate Cox analysis was performed.Results: By permutation testing, we selected 92 genes demonstrated distinct expression patterns differing significantly between recurrence cases and recurrence-free cases. Our prediction method, using the 20 top-ranked genes, correctly predicted the early intrahepatic recurrence for 29 of 40 cases within the validation group, and the odds ratio was 6.8 (95%CI 1.7-27.5, P = 0.010). The 2-year recurrence rates in the patients with the good signature and those with the poor signature were 29.4 and 73.9%, respectively. Multivariate Cox analysis revealed that molecular-signature was an independent indicator for recurrence (hazard ratio 3.82, 95%CI 1.44-10.10, P = 0.007).Conclusions: Our molecular-based prediction method using 20 genes is clinically useful to predict early recurrence of HCC. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.