HK2、STAT3在病毒性肝炎诱发肝癌中的组织芯片研究  

A Tissue Microarray Study of HK2 and STAT3 in Viral Hepatitis Related-hepatocellular Carcinoma

作　　者：李嫚 张铁英 晋瑞[2] 刘正稳[3] LI Man;ZHANG Tie-ying;JIN Rui;LIU Zheng-wen(Department of Internal Medicine,Xi＇an No.3 Hospital,Xi＇an 710018,China;Department of Radiology,Second Affiliated Hospital of Xi＇an Jiaotong University,Xi＇an 710004,China;Department of Infectious Diseases,First Affiliated Hospital of Xi＇an Jiaotong University,Xi＇an 710061,China)

机构地区：[1]西安市第三医院内科 [2]西安交通大学医学院第二附属医院放射科 [3]西安交通大学医学院第一附属医院传染科

出　　处：《标记免疫分析与临床》2018年第8期1218-1222,共5页Labeled Immunoassays and Clinical Medicine

基　　金：西安市科技计划项目[编号:2017113SF/YX007(16)]

摘　　要：目的探讨已糖激酶2(hexokinase 2,HK2)、转录激活因子3(signal transducer and activator of transcription 3,STAT3)在病毒性肝炎诱发肝癌中的机制。方法应用组织芯片技术和免疫组织化学方法检测在肝炎病毒感染、肝癌和肝纤维化组织中HK2和STAT3的表达,并对二者的表达进行相关性分析,同时我们还根据肝癌细胞的分化对HK2和STAT3的表达和分布进行了统计学相关分析研究。结果通过计数细胞阳性率,发现乙肝病毒感染的肝癌组织中HK2的表达强度与STAT3的表达强度一致(P=0.141)。乙肝病毒感染的肝癌组织中HK2表达上调(约50%),显著高于肝癌(30%)、丙肝(10%)、肝纤维化(乙肝病毒感染)(30%)以及正常组织(20%)(P<0.05)。STAT3在乙肝病毒感染肝癌组织中主要分布于细胞浆和胞核(90%),显著高于肝癌(65%)、丙肝(40%)、肝纤维化(乙肝病毒感染)(30%)以及正常组织(30%)(P<0.05)。HK2与STAT3表达的相关性分析结果显示,在同一乙肝病毒感染的肝癌组织中STAT3的表达强度与HK2的表达强度一致;肝癌、丙肝、肝纤维化组织中STAT3的表达强度与HK2的表达强度差异具有统计学意义(P<0.05)。HK2的高表达与肝癌的分化无显著相关性。结论 HK2和STAT3的活化与乙肝病毒感染的肝癌发生和发展相关,在乙肝促肝癌的过程中HK2起到了重要作用,而STAT3被活化后定位于细胞核中,极有可能促进了HK2的表达。本研究提示HK2和STAT3在肝癌和乙肝病毒感染肝细胞的恶性转化过程中可能发挥重要作用,为肝癌的发生机制提出新的理论和作用靶位。Objective To study the functional mechanism of hexokinase 2 （ HK2 ） and signal transducer and activator of transcription 3 （ STAT3 ） in viral hepatitis related- hepatocellular carcinoma （ HCC ）. Methods The expressions of HK2 and STAT3 in hepatitis virus infection, viral hepatitis related-HCC and liver fibrosis tissues were detected by tissue microarray technique and immunohistochemistry. And a correlation analysis of the expression of HK2 and STAT3 was conducted. We also analyzed the expression and distribution of HK2 and STAT3 based on the differentiation of HCC tissues. Results By counting the positive rates of cells, the expression of HK2 in HBV related-HCC tissues was consistent with that of STAT3 （ P = 0. 141 ）. The expression of HK2 in HBV related-HCC was increased（ about 50% ）, significantly higher than that of HCC（ 30% ）, hepatitis C （ 10% ）, HBV related- liver fibrosis （ 30% ） and normal tissue （ 20% ） （ P 〈 0.05 ）. STAT3 was mainly distributed in cytoplasm and nucleus（90% ）in HBV related-HCC tissues, significantly higher than HCC （ 65 % ）, hepatitis C （40 % ）, HBV related- liver fibrosis （ 30 % ） and normal tissue （ 30 % ） （ P 〈 0.05 ）. The correlation analysis between HK2 and STAT3 expression showed that the expression of STAT3 was consistent with HK2 in HBV related-HCC tissues. The expressions of STAT3 and HK2 in HCC, hepatitis C and liver fibrosis were significantly different （ P〈 0. 05 ）. There was no significant correlation between the high expression of HK2 and the differentiation of HCC. Conclusion The activation of HK2 and STAT3 is related to the occurrence and development of HBV infection. HK2 plays an important role in the process of HBV promoting HCC, while STAT3 is located in the nucleus after activation, and it may promote the expression of HK2. This study suggests that HK2 and STAT3 may play an important role in the malignant transformation of HBV related-HCC, and provide a novel target for the pathogenesis of HCC.

关 键 词：肝癌 病毒性肝炎 转录激活因子3(STAT3) 己糖激酶2(HK2) 

分 类 号：R735.7[医药卫生—肿瘤] R512.6[医药卫生—临床医学]