乙肝相关性肝细胞癌患者血清外泌体miR-1290水平的变化及其诊断价值

Change in serum level of exosomal miR-1290 in patients with hepatitis B virus related hepatocellular carcinoma and its diagnostic value

目的:探讨乙型肝炎病毒(HBV)相关性肝细胞癌(HCC)患者血清外泌体miR-1290水平的变化及其诊断价值。方法:收集31例HBV相关HCC患者,20例HBV携带患者,20例乙型肝炎肝硬化患者以及19例健康体检者的血液样本,分离纯化血清外泌体并鉴定,用RT-PCR检测外泌体miR-1290水平。利用ROC曲线评价外泌体miR-1290对HBV相关HCC的诊断效能。结果:纯化提取的样品中含有大量外泌体颗粒,并且具备外泌体的典型特性。与健康个体比较,外泌体miR-1290水平在HBV携带患者中未见明显差异(P>0.05)在HBV相关HCC患者中明显升高(P<0.001),且晚期HCC患者高于早期HCC患者(P=0.036),而在乙型肝炎肝硬化患者中明显降低(P=0.006)。外泌体miR-1290的ROC曲线的曲线下面积(AUC)为0.82(95%CI=0.73～0.91),具有较好的特异性(88.1%),且其诊断效能优于AFP(AUC=0.792)。结论:血清外泌体miR-1290在HBV相关HCC患者中升高,对HBV相关HCC具有较好的诊断效能,并有望成为诊断HBV相关HCC的血清学标志物。

Objective: To investigate the change in serum exosomeal miR-1290 level in patients with hepatitis B virus(HBV) related hepatocellular carcinoma(HCC) and its diagnostic value. Methods: The blood samples from 31 patients with HBV-related HCC, 20 HBV carriers, 20 patients with hepatitis B induced liver cirrhosis, and 19 subjects undergoing health maintenance examination were collected. The serum exosomes were isolated and purified and then identified. The expression levels of exosomal miR-1290 were determined by RT-PCR. The diagnostic efficacy of exosomal miR-1290 for HBV-related HCC was evaluated using the ROC curve.Results: The purified samples contained a large number of exosomal particles with the typical characteristics of the exosomes. Compared with healthy individuals, the exosomal miR-1290 level showed no significant difference in HBV carriers(P>0.05), and was significantly elevated in patients with HBV-related HCC(P<0.001), in advanced stage HCC patients was significantly higher than in early stage HCC patients(P=0.036), but was significantly decreased in patients with hepatitis B induced liver cirrhosis(P=0.006). The area under the curve(AUC) of the ROC of exosomel miR-1290 for diagnosis of HBV-related HCC was 0.82(95% CI=0.73 0.91), with good specificity(88.1%), and its diagnostic efficiency was higher than that of AFP(AUC=0.792).Conclusion: Serum level of exosomal miR-1290 is increased in patients with HBV-related HCC, and it has better diagnostic efficacy for HBV-related HCC. It is hopeful to become a serological marker for the diagnosis of HBVrelated HCC.