TIMP-3在肝癌组织中的表达及其与肿瘤侵袭转移的关系

摘要

AIM: To detect the levels of tissue inhibitor of metalloproteinase - 3 ( TIMP - 3 ) in both plasma and the tissue of hepatocellular carcinoma ( HCC ), and to elucidate their association with clinical features.METHODS: Plasma protein levels of TIMP - 3 in 56 HCC patients and 30 cases of controls were detected by ELISA.The mRNA and protein levels of TIMP - 3 in 30 HCC tissue samples with their portal vein tumor embolus and lymphatic metastasis tissues, and in normal liver tissues from 30 controls were detected by RT - PCR and Western blotting.The relationship between mRNA and protein levels and their clinic - pathological data were analyzed.RESULTS: The plasma TIMP - 3 protein levels in the extrahepatic metastasis patients were obviously lower than those in the non - extrahepatic metastasis patients ( P ＜ 0.05 ).The mRNA levels of TIMP - 3 in normal liver, carcinoma in situ, portal vein tumor embolus and lymphatic metastasis tissues were 0.78 ± 0.09, 0.52 ± 0.09 , 0.42 ± 0.07 and 0.40 ± 0.08 , respectively, with significant differences among them ( P ＜0.05 ).The protein levels of TIMP - 3 in these 4 kinds of tissues were 115.08 ± 8.60, 77.04 ± 8.83 , 64.43 ±3.80 and 62.80 ± 3.73, respectively, also with significant differences among them ( P ＜ 0.05 ).CONCLUSION : The expression of TIMP - 3 significantly decreases in the carcinoma in situ tissues of HCC patients, and decreases more obviously in the portal vein tumor embolus and lymphatic metastasis tissues, indicating that low expression of TIMP - 3 may play an important role in HCC invasiveness and metastasis.%目的:检测金属蛋白酶-3组织抑制剂(TIMP-3)在肝细胞癌患者血浆和肿瘤及正常肝组织中的表达并探讨其临床意义.方法:收集56例肝细胞癌患者和30例对照组的血浆,从肿瘤大小、分化程度、肝外转移、门脉转移及淋巴转移几个因素比较TIMP-3蛋白表达水平;取手术标本包括30例原位癌组织标本、30例门脉癌栓组织标本、30例淋巴转移组织标本以及30例肝正常组织标本,采用RT-PCR和Western blotting法检测各个样本的TIMP-3mRNA及蛋白表达,结合临床病理资料分析其意义.结果:(1)有肝外转移患者的血浆TIMP-3蛋白表达水平明显低于无肝外转移者(P<0.05).(2)TIMP-3 mRNA在原位肝癌组织中表达水平为0.52±0.09,在门脉癌栓组织中的表达水平为0.42±0.07,在淋巴转移灶的表达水平为0.40±0.08,在正常肝组织中表达水平为0.78±0.09;3组肿瘤组织与正常肝组织相比,TIMP-3 mRNA表达均降低,显著差异(P＜0.01).(3)TIMP-3蛋白在原位肝癌组织中表达水平为77.04±8.83,在门脉癌栓组织中的表达水平为64.43±3.80,在淋巴转移灶的表达水平为62.80±3.73,在正常肝组织中表达水平为115.08±8.60;3组肿瘤组织与正常肝组织相比TIMP-3蛋白表达均降低,显著差异(P＜0.01).结论:肝癌患者血浆和组织中TIMP-3的表达水平明显下降,在转移灶中的表达下降更显著,提示TIMP-3的低表达与肿瘤细胞的侵袭转移能力有关.