Identification and validation of a novel gene signature associated with the recurrence of human hepatocellular carcinoma
Identification and validation of a novel gene signature associated with the recurrence of human hepatocellular carcinoma
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DOI：
10.1158/1078-0432.ccr-06-2236
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发表时间：
2007-11-01
影响因子：
11.5
通讯作者：
Hui, Kam M.
中科院分区：
文献类型：
--
作者：
Wang, Sulk Mei;Ooi, London Lucien P. J.;Hui, Kam M.
目的：为了通过在诊断时准确识别原发性肝癌治疗后有复发风险的患者来改善人类肝细胞癌（HCC）的临床管理。实验设计：诊断时可用的两个临床病理学变量，血管浸润和肝硬化，以及使用Affytelium人类HG-U133 A和HG-U133 B寡核苷酸探针阵列的分子谱分析，用于识别复发性HCC疾病。HCC患者在诊断时临床表现为血管浸润和肝硬化，在6至35个月内复发率很高（78-83%）。相比之下，大多数没有血管浸润和肝硬化的HCC患者（80-100%）仍然没有疾病。然而，无论是血管侵犯或肝硬化的肝癌患者复发疾病的风险不能准确地确定。使用23例血管浸润或肝硬化的HCC患者作为训练集，获得了57个基因签名，并且可以预测诊断时的复发疾病，对于25例血管浸润或肝硬化的HCC患者的完全独立的测试集，准确率为84%（灵敏度86%，特异性82%）。经进一步分析，试验组中预测复发或不复发的患者的无病率有显著差异（P = 0.002）。我们提供的数据表明，通过整合部分根治性肝切除术后HCC患者诊断时的血管浸润和肝硬化状态以及一种新的57成员基因标签，我们可以准确地对具有不同复发风险的HCC患者进行分层。
Purpose: To improve the clinical management of human hepatocellular carcinoma (HCC) by accurate identification, at diagnosis, of patients at risk of recurrence after primary treatment for HCC.Experimental Design: Two clinicopathologic variables available at diagnosis, vascular invasion and cirrhosis, together with molecular profiling using Affymetrix human HG-U133A and HG-U133B oligonucleotide probe arrays, were used to identify recurrent HCC disease.Results: HCC patients presented clinically at diagnosis with vascular invasion and cirrhosis showed a high rate (78-83%) of developing recurrent disease within 6 to 35 months. In comparison, most of the HCC patients (80-100%) without vascular invasion and cirrhosis remained disease-free. However, the risk of recurrent disease for HCC patients with either vascular invasion or cirrhosis could not be accurately ascertained. Using a pool of 23 HCC patients with either vascular invasion or cirrhosis as training set, a 57-gene signature was derived and could predict recurrent disease at diagnosis, with 84% (sensitivity 86%, specificity 82%) accuracy, for a totally independent test set of 25 HCC patients with either vascular invasion or cirrhosis. On further analysis, the disease-free rate was significantly different between patients that were predicted to recur or not to recur in the test group (P = 0.002).Conclusion: We have presented data to show that by incorporating the status of vascular invasion and cirrhosis available at diagnosis for patients with HCC after partial curative hepatectomy and a novel 57-member gene signature, we could accurately stratify HCC patients with different risks of recurrence.