A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients.
A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients.
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DOI：
10.1158/0008-5472.can-10-2607
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发表时间：
2010-12-15
期刊：
影响因子：
11.2
通讯作者：
Wang XW
中科院分区：
文献类型：
--
作者：
Roessler S;Jia HL;Budhu A;Forgues M;Ye QH;Lee JS;Thorgeirsson SS;Sun Z;Tang ZY;Qin LX;Wang XW
肝细胞癌（HCC）患者在接受根治性治疗后经常发生转移相关复发。目前，识别具有高复发风险的患者具有挑战性，这将需要额外的治疗。在这项研究中，我们试图分析一个最近开发的转移相关的基因标签，其效用在预测肝癌生存使用两个独立的队列，共386例接受根治性切除术的患者。队列1包含247例使用Affymetrix平台分析的主要HBV阳性病例，而队列2包含139例使用NCI Oligo Set微阵列平台分析的混合病因病例。我们采用了一种具有训练、测试和独立交叉验证策略的生存风险预测算法，发现基因签名可预测总体和无病生存期。重要的是，独立于临床特征和微阵列平台显著预测风险。此外，生存预测在早期疾病患者中是成功的，例如小的（直径<5 cm）和孤立性肿瘤，并且特征预测早期复发风险（<2年）特别好，特别是当与血清甲胎蛋白或肿瘤分期相结合时。总之，我们已经在两个具有混合病因和种族的独立队列中证明了转移基因签名是预测HCC结果的有用工具，表明该分类器的通用性。我们建议使用该分类器作为分子诊断测试，以评估HCC患者在手术切除后2年内发生肿瘤复发的风险，特别是对于那些早期肿瘤和孤立性表现的患者。
Metastasis-related recurrence often occurs in hepatocellular carcinoma (HCC) patients who receive curative therapies. At present, it is challenging to identify patients with high risk of recurrence, which would warrant additional therapies. In this study, we sought to analyze a recently developed metastasis-related gene signature for its utility in predicting HCC survival using two independent cohorts consisting of a total of 386 patients who received radical resection. Cohort-1 contained 247 predominantly HBV-positive cases analyzed with an Affymetrix platform, while cohort-2 contained 139 cases with mixed etiology analyzed with the NCI Oligo Set microarray platform. We employed a survival risk prediction algorithm with training, test, and independent cross-validation strategies and found that the gene signature is predictive of overall and disease-free survival. Importantly, risk was significantly predicted independently of clinical characteristics and microarray platform. In addition, survival prediction was successful in patients with early disease, such as small (<5 cm in diameter) and solitary tumors, and the signature predicted particularly well for early recurrence risk (<2 years), especially when combined with serum alpha fetoprotein or tumor staging. In conclusion, we have demonstrated in two independent cohorts with mixed etiologies and ethnicity that the metastasis gene signature is a useful tool to predict HCC outcome, suggesting the general utility of this classifier. We recommend the use of this classifier as a molecular diagnostic test to assess the risk that an HCC patient will develop tumor relaps within 2 years after surgical resection, particularly for those with early stage tumors and solitary presentation.