肝癌患者血清乙肝病毒特异性miRNAs水平指标检测与术后肿瘤复发的相关性研究

The Relationship between Expression of Serum Hepatitis B Virus (HBV) -specific miRNAs and the Recurrence after Surgical Resection for Patients with Hepatocellular Carcinoma

目的:HBV感染患者血清中HBV相关miRNAS的表达水平会出现变化,分析乙肝病毒特异性miRNAs在乙肝肝癌(hepato-cellular carcinoma,HCC)患者血清中的表达水平与术后肿瘤复发的关系。方法:采用实时荧光定量RT-PCR(Real-time RT-PCR)检测38例乙肝肝癌患者手术前后血清乙肝病毒特异性miRNAs(miR-122和miR-22)的表达。分析血清乙肝病毒特异性miRNAs的表达水平与肝癌切除术后的预后与复发的关系。结果:乙肝肝癌患者血清miR-122和miR-22明显高于良性肝病和正常对照组(P<0.01)。手术前后血清miR-122和miR-22的表达差异显著(P<0.01)。乙肝肝癌患者血清miR-122和miR-22表达的高低与HBVDNA、肝硬化、AFP、肿瘤大小、病理分化、TNM分级有关(P<0.05)。血清miR-122和miR-22低表达组的复发转移率显著低于高表达组(P<0.01)。结论:miR-122和miR-22在乙肝肝癌患者血清中表达上调与肝癌复发转移率高和预后差密切相关,提示其可能是一个潜在的HCC预后分子标志物。

Objective： To investigate the expression of Hepatitis B Virus （HBV）-specific miRNAs in serum of HBV associated hepatocellular carcinoma （HCC） patients, and to demonstrate its relationship with clinicopathological features and prognosis of HCC. Methods： Theexpression levels of HBV-specific miRNAs （miR-122 and miR-22） in the serum were measured by reverse transcription polymerase chain reaction （RT- PCR）. The correlations between serum HBV-specific miRNAs expression and clinicopathological features and prognosis were analyzed. Results： I-IBV associated HCC patients had significantly higher miR-122 and miR-22 levels than benign diseases and healthy controls. The expression ofmiR-122 and miR-22 in postoperative serum was significantly different from that of preoperative serum. The expression level of serum miR-122 and miR-22 had a close correlation with HBV DNA, liver cirrhosis, AFP level, tumor size,tumor thrombi, histological differentiation, TNM classification （P〈0.05）. The survival time of HCC patients with a lower miR-122 and miR-22 expression levels were longer than those with a higher level, and the recurrent/metastatic of HCC patients with a lower miR-122 and miR-22 expression levels were also lower than those with higher expression （P〈0.01）. Conclusion： The up-regulated expression of serum miR-122 and miR-22 are correlated with poor prognosis of HBV associated HCC, indicating that miR-122 and miR-22 can be used as a prognostic marker in I-IBV associated HCC patients.