miRNA-21/101/125a/195/200b在肝硬化、肝癌中的表达变化

目的观察microRNA(miRNA)-21/101/125a/195/200b在肝硬化、肝癌中的表达变化。方法收集患者肝组织样本,其中血管瘤6份、肝硬化10份,肝癌及癌旁组织14对;除血管瘤外,其余样本均HBsAg阳性。PCR检测各组miR-21、miR-101、miR-125a、miR-195、miR-200b的表达。采用Pearson相关性分析探索miR-101的表达与临床相应指标之间的相关性。结果与对照组相比,肝硬化组血小板(PLT)明显降低,凝血酶原时间(PT)延长、国际标准化比值(INR)升高,天门冬氨酸氨基转移酶(AST)和总胆红素(TBil)升高;HE染色、Masson染色及网状纤维染色显示符合肝硬化诊断。与肝硬化组相比,肝癌组白细胞(WBC)、PLT均有所升高,PT、INR降低,AST、TBil表达下降;与对照组、肝硬化组相比,肝癌组甲胎蛋白(AFP)表达显著升高,免疫组化染色符合肝癌诊断。PCR检测miRNA的表达,与对照组相比,miR-101、miR-195在肝硬化组中的表达下降;与癌旁组织相比,miR-21在肝癌中的表达升高,miR-101、miR-195的表达则显著降低。miR-125a、miR-200b的表达在各组间无明显变化。Pearson相关性分析发现miR-101与PLT表达水平呈正相关,相关系数为0.375。结论 miR-101在肝硬化、肝癌组织中表达降低,且与血小板水平呈正相关,提示miR-101是慢性肝病的负调控因子。

Expression of miRNA-21/101/125a/195/200b in hepatic cirrhosis and carcinoma

Objective To investigate the differential expression of microRNA (miRNA, miR) 21/101/125a/195/200b in patients with hepatic cirrhosis and hepatocellular carcinoma (HCC).Methods Liver samples of hemangioma (6 cases), cirrhosis (10 cases) and HCC and adjacent tissues (14 pairs) were collected, in which hepatitis B surface antigen (HBsAg) was positive except samples from hemangioma.Real-time polymerase chain reaction (RT-PCR) was applied to detect the expression of miR-21/101/125a/195/200b, respectively.Pearson correlation analysis was carried out between expression of miR-101 and the related clinical indexes.Results In cirrhosis group, levels of prothrombin time (PT), international normalized ratio (INR), aspartate transaminase (AST) and serum total bilirubin (TBiL) were significantly higher than those in hemangioma group, while blood platelet (PLT) was significantly lower. Hematoxylin and eosin (HE) staining, Masson staining and reticular fiber staining were all consistent with the diagnosis of cirrhosis. In HCC group, white blood cell (WBC) and PLT were increased, while levels of PT, INR, AST and TBil were decreased compared with those in cirrhosis group. Using immunohistochemical staining, alpha fetal protein was significantly higher in HCC group than that in hemangioma or cirrhosis groups, which was confirmed the diagnosis of HCC in turn. Compared with hemangioma group, miR-101 and miR-195 were down-regulated in cirrhosis group. Compared with the para-carcinoma tissues, miR-21 was up-regulated in HCC tissue, while miR-101 and miR-195 were down-regulated. There were no statistical difference in the expression of miR-125a and miR-200b among the three groups. miR-101 was positively correlated with the expression of PLT with coefficient of 0.375. Conclusion miR-101 is remarkably decreased in both HBV-related cirrhosis and HCC, which is positively correlated with PLT. It suggests that miR-101 might be a negative regulator of chronic liver disease.