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目的 :探讨外周血循环miR-152在乙型肝炎病毒阳性肝细胞癌中的表达变化及其临床应用价值。方法:采用病例对照研究方法,对2014年5月至2015年1月在山东大学齐鲁医院住院的36例HBV阳性原发性肝细胞肝癌,28例HBV阳性肝硬化,28例乙型肝炎及28例健康对照进行研究,应用RT-PC R方法测定血清miR-152的相对表达量,分析其与性别、年龄、肿瘤大小、分化程度等病理参数的关系,并同时用电化学发光分析仪检测其甲胎蛋白浓度。应用受试者工作曲线(ROC)分析循环miR-152的表达与HBV阳性肝细胞癌诊断的敏感性及特异性。采用SPSS19.0统计学软件进行数据分析,所有计量资料均先进行单样本K-s检验正态性分布,采用单因素方差分析进行多组间均数的比较,组间均数比较采用SN K-q检验和独立样本t检验。结果:外周血循环miR-152表达在肝硬化组(0.392±0.255)、肝细胞癌患者组(0.315±0.161)与肝炎组(0.603±0.247)和健康对照组(1.157±0.569)差异具有统计学意义(P<0.01),且其表达与HBV阳性肝细胞癌的分化程度密切相关(P<0.01),而与性别、年龄、肿瘤大小及TNM分期无显著统计学意义(P>0.05),经AUC-ROC曲线分析其作为标志物检测HBV阳性肝细胞癌时诊断效能[0.933(95%C I:0.841~0.980)]显著高于甲胎蛋白[0.757(95%C I:0.634~0.855)](P<0.01),比甲胎蛋白联合检测诊断效能[0.973(95%C I:0.898~0.996)]显著提高(P<0.01)。结论:外周血循环miR-152与HBV阳性肝细胞癌进展相关,与AFP联合检测具有更高的灵敏度和特异性,有望成为HBV阳性肝细胞癌的生物标志物。
Objective: To investigate the changes of peripheral blood circulating miR-152 in Hepatitis B virus positive hepatocellular carcinoma and its clinical value. Methods: A case-control study was conducted on 36 patients with HBV-positive primary hepatocellular carcinoma, 28 patients with HBV-positive cirrhosis, 28 patients with hepatitis B and 28 patients with hepatitis B who were hospitalized in Shandong Qilu Hospital from May 2014 to January 2015 Cases of healthy control study, the relative expression of serum miR-152 was measured by RT-PC R method, and its relationship with pathological parameters such as gender, age, tumor size, degree of differentiation and other parameters were detected by electrochemiluminescence analyzer Alpha-fetoprotein concentration. The receiver operating characteristic curve (ROC) was used to analyze the sensitivity and specificity of circulating miR-152 in the diagnosis of HBV-positive hepatocellular carcinoma. SPSS 19.0 statistical software for data analysis, all measurement data were first single-sample Ks test normal distribution, using single-factor analysis of variance between groups of mean comparison, comparison between groups using SN Kq test and Independent sample t test. Results: The expression of miR-152 in peripheral blood of patients with cirrhosis (0.392 ± 0.255), hepatocellular carcinoma (0.315 ± 0.161) and hepatitis (0.603 ± 0.247) and healthy controls (1.157 ± 0.569) was statistically significant (P <0.01), and its expression was closely related to the differentiation degree of HBV-positive hepatocellular carcinoma (P <0.01), but not with the gender, age, tumor size and TNM stage (P> 0.05) -ROC curve was significantly higher than that of AFP [0.757 (95% CI: 0.634-0.885)] when used as a marker in detecting HBV-positive HCC (0.933, 95% CI: 0.841-0.980) 0.01), which was significantly higher than that of AFP (0.973 (95% CI: 0.898-0.996)] (P <0.01). Conclusion: miR-152 in peripheral blood is associated with the progress of HBV-positive hepatocellular carcinoma. Combined with the detection of AFP, miR-152 has higher sensitivity and specificity and is expected to become a biomarker of HBV-positive hepatocellular carcinoma.