乙型肝炎病毒相关肝癌组织及外周血膜联蛋白A2异常表达的临床意义  

Overexpression of annexin A2 in hepatic tissue and serum of patients with HBV-associated hepatocellular carcinoma

作　　者：陈雯[1] 张海健[2] 顾星[2] 时运[2] 钱琦[2] 姚登福[2] 陆少林[2] 

机构地区：[1]南通大学附属医院检验科,江苏省南通市226001 [2]南通大学附属医院临床医学研究中心,江苏省南通市226001

出　　处：《世界华人消化杂志》2014年第9期1207-1213,共7页World Chinese Journal of Digestology

基　　金：国家国际科技合作专项基金资助项目;No.2013DFA32150;南通市社会事业科技创新与示范基金资助项目;No.2012034~~

摘　　要：目的:探讨乙型肝炎病毒(hepatitis B virus,HBV)感染对肝癌(hepatocellular carcinoma,HCC)组织及外周血中膜联蛋白A2(annexinA2,ANXA2)表达的影响.方法:以自身配对法收集30例术后肝癌组织、癌旁组织和远癌组织,以Western blot法和免疫组织化学法分析肝组织ANXA2表达与细胞中分布;并以生物素标记的HBV DNA探针检测肝组织中HBV DNA,以实时定量PCR技术分析肝组织ANXA2 mRNA转录与表达水平;以ELISA法定量肝病患者血ANXA2水平,分析其临床价值.结果:肝组织ANXA2表达定位于癌细胞的胞浆和胞膜,癌旁组织定位于胞浆;癌组织显著高于癌旁组织(F=498.221,P<0.001),远癌组织则未见明显表达;癌灶组织中ANXA2基因呈过转录状态,显著高于癌旁与远癌组织;在HBV阳性肝癌组织中,ANXA呈中等至强阳性全数表达,在HBV阴性肝癌组织ANXA呈低阳性表达,组间差异显著(Z=4.933,P<0.001).血ANXA2水平,肝癌患者显著高于良性肝病各组(P<0.01),其表达与HBV感染(t=6.820,P<0.001)、伴肝外转移(t=3.191,P=0.002)、门静脉癌栓(t=2.859,P=0.005)、中低程度分化和TNM分期间显著相关(P<0.01),但与患者性别、年龄、肿瘤大小和甲胎蛋白(alpha-fetoprotein)水平间未见明显相关;血ANXA2与AFP联检,其诊断阳性率为96.5%.结论:HBV相关肝癌ANXA2过表达,有助于HCC诊断和发病机制解析.AIM： To investigate the expression of annexin A2 （ANXA2） in hepatic tissue and serum of hep- atitis B virus （HBV）-associated hepatocellular carcinoma （HCC）. METHODS： ANXA2 expression in HCC, tumor- adjacent precancerous and distal normal tissues was analyzed by real-time polymerase chainreaction （PCR） and Western blot. The cellular localization of ANXA2 in these specimens was detected by immunohistochemistry, and hepatic HBV DNA was detected by in sittt hybridization technique. Levels of serum ANXA2 in patients with HCC or benign liver diseases were quanti- tatively detected by enzyme-linked immunosor- bent assay （ELISA）. RESULTS： Hepatic ANXA2 expression was lo- calized in the cytoplasm and membrane of cells in cancerous tissues, and cytoplasm of cells in tumor adjacent cancerous tissues, but was unde- tectable in distal normal tissues （F= 498.221, P 〈 0.001）. Overexpression of ANXA2 mRNA in can- cerous tissues was significantly higher than that in tumor adjacent cancerous or distal normal tis- sues. ANXA expression was moderate to strong in cancerous tissues with HBV replication, but low in cancerous tissues without HBV replica- tion （Z = 4.933, P 〈 0.001）. Circulating ANXA2 levels in HCC patients were significantly higher than those in any group of other liver diseases （P 〈 0.01） except the metastatic liver cancer group. Serum levels of ANXA2 in patients with HCC were associated with HBV infection （t = 6.820, P 〈 0.001）, extrahepatic metastasis （t = 3.191, P = 0.002）, presence of portal vein thrombus （t = 2.859, P = 0.005）, lower differentiation degree and TNM stage （P 〈 0.01）, but not with patient sex, age, size or AFP level. Combined detection of serum ANXA2 and AFP substantially im- proved the diagnostic efficiency （96.5%）. CONCLUSION： Abnormal expression of ANXA2 in HBV-related HCC is useful for diagnosing HCC and understanding its pathogenesis.

关 键 词：肝细胞癌 膜联蛋白A2 表达 诊断 乙型 肝炎病毒感染 

分 类 号：R735.7[医药卫生—肿瘤]