ATF3 MMP-2及maspin在肝细胞癌中的表达及意义  

Expression and Significance of ATF3, MMP-2 and Maspin in Hepatocellular Carcinoma

作　　者：余茂武[1] 臧盛兵[1] 黄爱民[1] 高凌云[1] 刘景丰[2] 

机构地区：[1]福建医科大学基础医学院病理学系福建医科大学肿瘤研究室,福州市350004 [2]福建医科大学附属第一医院肝病中心

出　　处：《中国肿瘤临床》2009年第13期759-763,共5页Chinese Journal of Clinical Oncology

基　　金：福建省教育厅科技项目基金资助(编号:JA04193);教育部科学技术研究重点项目(编号:205077)~~

摘　　要：目的:检测ATF3、MMP-2及maspin在肝细胞癌(hepatocellular carcinoma,HCC)组织芯片中的表达情况,探讨ATF3、MMP-2及maspin表达与HCC发生、发展的关系及其意义。方法:对手工制作组织芯片的方法进行改良,构建含HCC、癌旁肝组织、远癌肝组织、正常肝组织及肝内转移灶的组织芯片,应用免疫组织化学和图像分析技术检测ATF3、MMP-2及maspin的相对表达量,并分析其与各临床病理参数的关系及其意义。结果:ATF3及MMP-2在HCC中表达明显高于癌旁肝组织、远癌肝组织及正常肝组织(P<0.01),而maspin在HCC中的表达明显低于癌旁肝组织、远癌肝组织及正常肝组织(P<0.01)。ATF3蛋白在女性HCC患者中的表达量高于男性患者(P<0.01),在转移组中表达高于无转移组(P<0.01);MMP-2蛋白随HCC病理学分级的升高,相对表达量降低(P<0.05),MMP-2蛋白在直径大于3cm的HCC中的相对表迭量高于直径小于3cm的表达量(P<0.05),包膜侵犯组高于无包膜侵犯组(P<0.05),肝内转移灶表达量高于原发灶(P<0.05);ATF3和MMP-2均随着HCC的进展表达量逐渐增高,maspin却随着HCC病理学分级的升高,相对表达量降低(P<0.05)。ATF3蛋白表达与MMP-2表达呈正相关(r_s=0.13,P<0.05),与maspin表达呈负相关(r_s=-0.23,P<0.01);MMP-2蛋白表达与maspm表达呈负相关(r_s=-0.17,P<0.01)。结论:在HCC组织中,ATF3、MMP-2及maspin的表达存在相关关系,ATF3、MMP-2高表达及maspin缺失表达与HCC的发生密切相关,他们可能在HCC发生发展、侵袭转移过程中发挥重要作用。选择性抑制ATF3有可能成为治疗HCC新的靶点。Objective： To detect the expression of ATF3, MMP-2 and maspin in hepatocellular carcinoma （HCC） and study the correlation of ATF3, MMP-2 and maspin expression with the progression of HCC. Meth- ods： Tissue chips were constructed using HCC, non-neoplastic adjacent liver tissues, non-neoplastic distant liver tissues, normal liver tissues and intrahepatic metastatic lesions. The expression of ATF3, MMP-2 and maspin was detected by immunohistochemistry and semi-quantitative image analysis. The correlation of ATF3, MMP-2 and maspin expression with clinicopathologic parameters of HCC was also analyzed. Results： The expression of ATF3 and MMP-2 in HCC was significantly higher than that in non-neoplastic adjacent liver tissues, non-neoplastic distant liver tissues and normal liver tissues （P〈0.01）, but the expression of maspin in HCC was significantly lower than that in non-neoplastic adjacent liver tissues, non-neoplastic distant liver tis- sues and normal liver tissues （P〈0.01）. The expression of ATF3 in HCC in female patients was significantly higher than that in male patients （P〈0.01）. The expression of ATF3 in HCC patients with intrahepatic metastasis was significantly higher than that in those without intrahepatic metastasis （P〈0.01）. The expression of MMP-2 was decreased as the histological grade increased （P〈0.05）. The expression of MMP-2 in HCC pa-tients with tumor larger than 3cm in diameter was higher than that in those with tumor less than 3cm in diameter （P〈0.05）. The expression of MMP-2 in HCC patients with capsule invasion was higher than that in those without capsule invasion （P〈0.05）. The expression of MMP-2 in primary HCC lesions was lower than that in corresponding metastatic lesions. With the progression of HCC, the expression of ATF3 and MMP-2 increased. The expression of maspin decreased as the histological grade increased （P〈0.05）. ATF3 expression was positively correlated with MMP-2 expression （rs=0.13,P〈0.05） and negatively correlate

关 键 词：肝细胞癌ATF3 MMP-2 MASPIN 组织芯片 

分 类 号：R735.7[医药卫生—肿瘤]