膜联蛋白A4在原发性肝细胞癌中的表达及其意义

Expression and clinicopathologic significance of annexin A4 in human hepatocellular carcinoma

目的观察膜联蛋白A4(Annexin A4)在不同肝细胞性肝癌(HCC)组织中的表达情况,探讨其临床病理意义。方法先应用RT-PCR验证ANX A4在不同类型肝组织中mRNA的表达,再应用免疫组织化学方法检测在15例正常肝组织、15例乙肝后肝硬化组织和63例不同表型肝癌组织标本中的表达,探讨其差异表达与临床病理资料之间的联系及其意义。结果(1)ANX A4 mRNA表达水平在肝硬化及肝癌组织中均比正常肝组织上调(P<0.05),但肝硬化组与肝癌组差异无统计学意义(P>0.05);(2)ANX A4蛋白阳性表达率正常肝组织为20%,乙肝后肝硬化组织为26.67%;在63例HCC中阳性率为49.21%,癌旁组织为61.90%,其中小肝癌阳性率为50.00%,大肝癌为64.29%,多发癌为28.57%,相应癌旁组织阳性率分别为50.00%、64.29%、66.67%。随着肝细胞的恶性转化并进展,ANX A4蛋白呈逐渐上调趋势,但当肿瘤出现侵袭转移时反而下调。与临床病理指标的相关性研究表明Annexin A4与HCC进展及侵袭相关。结论(1)从正常肝→肝硬化→肝癌组织,Annexin A4的mRNA表达水平逐渐上调;(2)ANXA4蛋白在HCC组织中的表达明显失调,其变化可能与HCC进展及侵袭相关。

Objective To investigate the differential expression of annexin A4 （ANX A4） protein in different phenotype of human hepatocellular carcinoma （HCC） tissues,and the correlative clinicopathologic significance was discussed. Methods The mRNA levels of ANX A4 in different liver tissues were validated by using semi-quantitative reverse transcription-polymerase chain reaction analysis （RT-PCR）, expressions of ANX A4 protein in different liver tissue specimens （15 cases normal liver tissues, 15 cases cirrhosis tissues post HBV hepatitis,63 cases different phenotype＇ s HCC tissues） were observed by immunohistochemistry assay. The relationship between the results of immunohisto- chemistry assay and the clinicopathologic parameters were studied. Results In mRNA level,the upregulation of ANX A4 in HCC tissues ANXA4 protein overexpressed in HCC tissues was higher than that in normal liver tissues （49.21% and 20% ,P =0. 040） ,and positive rate could be observed in different phenotype HCC tissues,that was 50.00% in small HCC,64.29% in large HCC,28.57% in multiple HCC,while the positive rate of para-tumorous tissues was 50.00% ,64.29% and 66. 67% ,respectively. The expression of ANXA4 up-regulated with the hepatocellular malignant metaplasia and progress. Expression of ANX A4 had a positive correlation with the tumor size and might be responsible for carcinogene- sis and progression of human hepatocellular carcinoma. Conclusion The mRNA level of ANXA4 was confirmed up-regulation in HCC and cirrhosis tissues compared to normal liver tissues. Unbalance of expression of ANX A4 could be observed in different phenotype HCC tissues. ANX A4 might take part in the process of carcinogenesis and progress of HCC.