A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis
A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis
复制标题
DOI：
10.1053/j.gastro.2006.09.014
复制
发表时间：
2006-12-01
期刊：
影响因子：
29.4
通讯作者：
Friedman, Scott L.
中科院分区：
文献类型：
--
作者：
Llovet, Josep M.;Chen, Yingbei;Friedman, Scott L.
背景与目的：2厘米大小的肝脏小结节很难通过放射学或病理检查表现出来。我们的目的是找出诊断早期肝细胞癌的分子标志。方法：采用实时定量逆转录聚合酶链式反应(RT-PCR)技术，检测17例异型增生结节(直径10 mm)、20例早期肝细胞癌(直径IS mm)、10例非肿瘤性肝硬变组织和10例正常肝组织中55个候选基因的转录水平。候选基因在20个晚期肝癌中通过定量RT-PCR和在75个样本中被免疫组织化学证实，并在一组独立的29个样本(发育不良结节[10]和小肝癌[19；直径，20 mm])中被证实。结果：TERT、GPC3、gankyrin、Survivin、TOP2A、LYVE1、E-cadherin、IGFBP3、PDGFRA、TGFA、Cyclin D1、HGF等12个基因在早期肝癌组织中的表达差异显著(P<0.05)。Logistic回归分析确定了3个基因集合，包括GPC3(肝细胞癌增加18倍，P=.01)、LYVE1(肝细胞癌减少12倍，P=.0001)和Survivin(肝细胞癌增加2.2倍，P=.02)，其判别准确率为94%。基因签名的有效性在一个预期的测试集中得到了证实。GPC3在所有肝细胞癌中均为阳性表达，在异型增生结节中均为阴性表达(22/22vs0/14，P
Background & Aims: Small liver nodules similar to 2 cm are difficult to characterize by radiologic or pathologic examination. Our aim was to identify a molecular signature to diagnose early hepatocellular carcinoma (HCC). Methods: The transcriptional profiles of 55 candidate genes were assessed by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) in 17 dysplastic nodules (diameter, 10 mm) and 20 early HCC (diameter, IS mm) from HCV cirrhotic patients undergoing resection/transplantation and 10 nontumoral cirrhotic tissues and 10 normal liver tissues. Candidate genes were confirmed by quantitative RT-PCR in 20 advanced HCCs and by immunohistochemistry in 75 samples and validated in an independent set of 29 samples (dysplastic nodules [10] and small HCC [19; diameter, 20 mm]). Results: Twelve genes were significantly, differentially expressed in early HCCs compared with dysplastic nodules (> 2-fold change; area under the receiver operating characteristic curve >= 0.8): this included TERT, GPC3, gankyrin, survivin, TOP2A, LYVE1, E-cadherin, IGFBP3, PDGFRA, TGFA, cyclin D1, and HGF. Logistic regression analysis identified a 3-gene set including GPC3 (18-fold increase in HCC, P=.01), LYVE1 (12-fold decrease in HCC, P=.0001), and survivin (2.2-fold increase in HCC, P=.02), which had a discriminative accuracy of 94%. The validity of the gene signature was confirmed in a prospective testing set. GPC3 immunostaining was positive in all HCCs and negative in dysplastic nodules (22/22 vs 0/14, respectively, P