肝细胞性肝癌膜联蛋白A2异常表达的临床病理学特征及意义

Clinicopathologic characteristics of Annexin A2 abnormal expression and its diagnostic value for hepatocellular carcinoma

目的分析膜联蛋白A2(ANXA2)在肝细胞性肝癌(HCC)患者中表达的临床病理学特征及对HCC的诊断价值。方法以自身配对法收集术后肝癌的癌灶、癌旁组织和远癌组织,以Western blot法检测组织中ANXA2的表达,以定量PCR分析ANXA2mRNA转录水平,以免疫组化法分析ANXA2在细胞中定位;分组收集肝癌、良性肝病患者和健康人群外周血,以ELISA法定量外周血中ANXA2表达水平。结果无论是ANXA2还是ANXA2mRNA,HCC癌灶组织中ANXA2表达显著高于癌旁和远癌组织(P<0.001);ANXA2在HCC癌灶组织中定位于胞质和胞膜,癌旁组织中定位于胞质,而远癌组织中未见明显表达;HCC患者血ANXA2表达水平,显著高于良性肝病或健康人群(P<0.01),但与转移性肝癌组间未见明显差异。临床病理学特征:血ANXA2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(P<0.001)和TNM分期相关(t=5.594,P<0.001),但与患者性别、年龄、肿瘤大小和AFP水平间未见明显相关;血ANXA2与AFP联合检测,可提高肝癌诊断阳性率(96.52%)。结论 ANXA2过表达有助于肝癌的诊断与鉴别。

Objective To investigate the clinicopathologic characteristics of Annexin A2 （ANXA2） expression in patients with HBV-related hepatoeellular carcinoma （HCC）and evaluate its diagnostic value for HCC. Methods The ANXA2 expression level in the HCC tissues and self-controlled precancerous tissues was analyzed by real time polymerase chain reaction（PCR） and Western blot,respectively. The cellular localization of ANXA2 in these specimens was detected by immunohistochemistry. The expression level of serum ANXA2 in the patients with HCC or benign liver disease was quantitatively detected by enzyme-linked immunosorbnent assay（ELISA）. Results ANXA2 was over-expressed in HCC tissues comparing with the self-controlled adjacent- and distant-cancerous tissues at protein or mRNA level. Circulating ANXA2 level in HCC patients was significantly higher than that of any group of other liver disease（ P 〈 0. 01 ）except metastatic liver cancer group. The abnormal expression of serum ANXA2 in HCC patients was correlated with H BV infection （ t = 6. 820, P 〈 0. 001 ）, extrahepatic metastasis （ t = 3.191, P = 0. 002）, and portal vein thrombus （ t = 2. 859, P = 0. 005 ）, but not with the patient sex, age, size or AFP level. The joint diagnosis of serum ANXA2 and AFP substantially improved the diagnostic efficiency（96. 52% ）. Conclusions The expression characteristics of ANXA2 really have good diagnostic potential for HCC.