Clinical Significance and Prognostic Value of microRNA Expression Signatures in Hepatocellular Carcinoma
Clinical Significance and Prognostic Value of microRNA Expression Signatures in Hepatocellular Carcinoma
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DOI：
10.1158/1078-0432.ccr-12-2728
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发表时间：
2013-09-01
影响因子：
11.5
通讯作者：
Wang, Hui-Yun
中科院分区：
文献类型：
--
作者：
Wei, Rongrong;Huang, Guo-Liang;Wang, Hui-Yun
目的：microRNAs（miRNAs）在肿瘤的发生、发展中起重要作用。本研究的目的是确定miRNA在肝细胞癌中的表达特征，并阐明其对肝细胞癌的临床意义。实验设计：肝细胞癌患者，接受肝切除术被随机分为训练集（60例）和测试集（50例）。另外56例患者作为独立队列。结果：建立了一个由10个下调和20个上调的miRNA组成的30-miRNA标签，用于区分训练集中的肝细胞癌和非癌肝组织，准确率为99.2%。该签名的分类准确率在测试集和独立队列中分别为97%和90%。在训练集中通过qRT-PCR验证30-miRNA标签中的四种miRNA的表达水平。然后选择20种miRNA在训练集中构建预后标记。在这20个miRNAs中，6个是危险因素，14个是保护因素。根据20种miRNAs建立一个计算预后指数的公式。Kaplan-Meier分析显示预后指数高的患者生存率明显低于预后指数低的患者。这在测试集和独立集中得到了验证。结论：本研究中发现的30-和20-miRNA标签为肝癌患者的诊断和预后提供了新的分子方法，并为阐明肝癌发生的分子机制提供了线索。(C)2013年AACR。
Purpose: MicroRNAs (miRNAs) play important roles in the development and progression of cancer. The aim of this study is to identify miRNA expression signatures in hepatocellular carcinoma and delineate their clinical significance for hepatocellular carcinoma.Experimental Design: Patients with hepatocellular carcinoma, undergoing hepatectomy were randomly divided into training set (60 patients) and test set (50 patients). Other 56 patients were used as an independent cohort. The miRNA expression levels were detected by microarray and verified by quantitative real-time reverse transcription-PCR (qRT-PCR).Results: A 30-miRNA signature consisting of 10 downregulated and 20 upregulated miRNAs was established for distinguishing hepatocellular carcinoma from noncancerous liver tissues in the training set with 99.2% accuracy. The classification accuracies of this signature were 97% and 90% in the test set and independent cohort, respectively. The expression level of four miRNAs in the 30-miRNA signature was verified by qRT-PCR in the training set. Twenty miRNAs were then selected to construct prognostic signature in the training set. Of the 20 miRNAs, six were risk factors and 14 were protective factors. A formula based on the 20 miRNAs was built to compute prognostic index. Kaplan-Meier analysis showed that patients with a higher prognostic index had a significantly lower survival than those with a low index. This was verified in the test and independent sets. Multivariate analysis indicated that the 20-miRNA signature was an independent prognostic predictor.Conclusions: The 30- and 20-miRNA signatures identified in this study should provide new molecular approaches for diagnosis and prognosis of patients with hepatocellular carcinoma and clues for elucidating molecular mechanism of hepatocarcinogenesis. (C) 2013 AACR.