外周血GPC3与PEG10 mRNA检测对肝细胞癌转移的诊断价值

Value of GPC3 and PEG10 mRNA in peripheral blood in diagnosis of metastasis in hepatocellular carcinoma

目的研究外周血磷脂酰肌醇蛋白聚糖3(GPC-3)与遗传印迹基因(PEG10)mRNA检测对肝细胞癌(HCC)转移的诊断价值。方法30例HCC患者分为HCC转移组(n=18)和HCC未转移组(n=12),另选取11例肝硬化患者作为对照。以SYBRGreenⅠ作为荧光信号,采用实时荧光定量聚合酶链反应(FQ RT-PCR)检测三组患者外周血GPC-3 mRNA和PEG10 mRNA表达,应用ROC曲线和诊断性能专用指标评价两者预测诊断及排除诊断的价值。结果HCC转移组GPC-3 mRNA和PEG10 mRNA表达显著高于HCC未转移组和肝硬化组(P<0.05);HCC未转移组与肝硬化组GPC-3 mRNA和PEG10 mRNA的表达比较差异无统计学意义。单项检测GPC-3 mRNA和PEG10 mRNA的诊断灵敏度分别为66.7%和72.2%,特异度均为91.7%,ROC曲线下面积(AUC)为0.748和0.812;两基因检测平行试验的灵敏度为90.7%,特异度为84.0%,阴性似然比为0.11,诊断准确率为83.3%;系列试验的灵敏度为60.5%,特异度为98.7%,阳性似然比为45.5,诊断准确率为73.3%。结论检测外周血GPC-3mRNA和PEG10 mRNA对估计肝癌有无血行播散和肝外转移有一定的价值,且PEG10 mRNA优于GPC-3 mRNA。两者联合系列试验有助于HCC外周血转移的预测诊断。

Objective To explore the value of glypican-3 （GPC-3） mRNA and paternally expressed 10 （PEG10） mRNA in peripheral blood in diagnosis of metastasis in hepatocellular carcinoma （HCC）. Methods With SYBR Green I as fluorescence signal, real-time fluorescent quantitative reverse transcription-polymerase chain reaction was employed to detect the expression of GPC-3 mRNA and PEG10 mRNA in peripheral blood from patients with HCC with metastasis （n = 8）, HCC without metastasis （n = 12） and hepatic cirrhosis （n = 11）, and receiver operator characteristics curve （ROC） and specific parameters were adopted to analyse their value in predictive and exclusive diagnosis. Results The expression of GPG-3 mRNA and PEG10 mRNA in HCC with metastasis was significantly higher than that in HCC without metastasis and in hepatic cirrhosis （P 〈 0.05）, while there was no significant difference in the expression of GPC-3 mRNA and PEG10 mRNA between HCC without metastasis and hepatic cirrhosis. In single test, the sensitivities in the differential diagnosis between HCC with metastasis and HCC without metastasis were 66.7% for GPC-3 mRNA and 72.2% for PEG10 mRNA, and the specifieities were 91.7% and 91.7%, respectively. The areas under ROC were 0. 748 for GPC-3 mRNA and 0. 812 for PEG10 mRNA. With two markers in parallel test, the sensitivity, specificity, negative likelihood and diagnostic accuracy were 90.7%, 84.0%, 0.11 and 83.3%, respectively. In serial test, the sensitivity, specificity, positive likelihood and diagnostic accuracy were 60.5%, 98.7%, 45.5 and 73.3%, respectively. Conclusion Detection of GPC-3 mRNA and PEG10 mRNA in peripheral blood may help to predict blood metastasis and extrahepatic metastasis of HCC, and PEG10 mRNA works better than GPC-3 mRNA. The serial test of GPC-3 mRNA and PEG10 mRNA is helpful to the predictive diagnosis of peripheral blood metastasis of HCC.