循环microRNA-152在HBV阳性肝细胞癌中的表达及临床应用

Expression level of serum circulating micro RNA-152 and its clinical significance in HBV positive hepatocellular carcinoma

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 discuss the variation of the expression of the circulating miR-152in the serum of patients with HBV positive hepatocellular carcinoma and its clinical significance. Methods： The case-control study was conducted in this research. We collected 36 serum samples from patients with HBV positive hepatocellular carcinoma who hospitalized in Qilu Hospital Shandong University during May 2014 to January 2015, 28 with hepatic cirrhosis, 28 with HBV hepatitis and 28 healthy individuals. Then we examined the expression of miR-152 in serum by RT-PCR and analyzed the association with gender, age, tumor size, differentiation and other pathological parameters. Meanwhile, the level of AFP in serum was detected by electrochemiluminescene analyzer. The ROC （receiver operating characteristic curve） was used to analyze the sensitivity and specificity of serum miR-152 expression with HBV positive hepatocellular carcinoma. The SPSS 19.0 statistical software was used for data analysis. All the measurement data was firstly analyzed by One-Sample K-S Test to analyze the Normal Distribution and mean comparison in groups was conducted with single factor variance analysis and the pair wise comparison was performed with SNK-q method and T-test for dependent samples. Results： The expression of the circulating miR-152 in cirrhosis （0.392 ±0.255）, patients with hepatocellular carcinoma group （0.315 ± 0.161） and hepatitis group （0.603±0.247） and healthy control group （1.157 ± 0.569） difference was statistically significant （P〈O.01）, and its expression is closely related to the degree of differentiation HBV positive HCC（P〈0.01）, but has no obviously statistical significance with sex, age, tumor size and TNM stage （P〉0.05）. By AUC-ROC curve analysis, area under ROC curve of miR-152 [0.933（95%CI：0.841-0.980）] was significantly higher than alpha-fetoprotein（AFP） [0.757（95%CI ：0.634-0.855）]（P〈0.01）, and what＇s more when miR-152 jointed with AFP the area under ROC curve [0.973（95%CI：0.898-0.996）] is significantly increased（P〈0.01）. Conclusion： The expression level of circulating miR-152 was associated with HBV positive HCC progression and jointly with the AFP test has a higher sensitivity and specificity, and furthermore miR-152 can be expected to become HBV positive HCC tumor biomarkers.