肝细胞癌组织缺氧诱导因子2α表达及其临床意义  

Expression and clinical significance of HIF-2α in hepatocellular carcinoma tissues

作　　者：尉洪龙 王付海[1] 修鹏[1] 田虎[1] 李杰[1] 刘锋[1] WEI Hong long;WANG Fu-hai;XIUPeng;TIAN Hu;LI Jie;LIU Feng(Department of Hepatobiliary Surgery,Shandong Provincial Qian f oshan Hospital,J inan 250014,P.R.China)

机构地区：[1]山东省千佛山医院肝胆外科,山东济南250014

出　　处：《中华肿瘤防治杂志》2018年第17期1222-1226,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：山东省医药卫生科技发展计划(2015WSB04031);山东省自然科学基金(ZR201702210502);山东省重点研发计划(2016GSF201108)

摘　　要：目的缺氧诱导因子2α(hypoxia-inducible factor-2α,HIF-2α)是肿瘤慢性缺氧反应中的关键性蛋白。本研究检测了缺氧条件下HIF-2α在肝癌细胞系中的表达,并进一步探讨了其在肝癌及癌旁组织中的表达及其临床意义。方法首先利用蛋白质印迹法检测缺氧条件下HIF-2α在不同肝癌细胞系中的表达情况;其次以2013-01-01-2014-12-31在山东省千佛山医院经手术及术后病理确诊的66例肝细胞癌患者为研究对象,应用免疫组织化学及蛋白质印迹法检测肝癌组织、癌旁组织中HIF-2α蛋白的表达,并分析了HIF-2α蛋白表达水平与肝细胞肝癌临床病理特征之间的关系。结果缺氧环境下HIF-2α在肝癌细胞系HepG2、Bel-7402、Huh-7和SMMC-7721中普遍表达升高。12例肝癌组织中HIF-2α的表达水平明显高于癌旁组织中HIF-2α的表达水平,差异有统计学意义,P<0.01。66例肝癌组织HIF-2α阳性表达43例,阳性率为65.2%;66例癌旁组织HIF-2α阳性表达15例,阳性率为22.7%;差异有统计学意义,P<0.01。肝癌组织HIF-2α表达水平与肝癌的TNM分期有关联,P=0.033。结论 HIF-2α在肝癌组织中高表达,并且HIF-2α阳性表达与肝癌的TNM分期有关联,提示HIF-2α与肝癌的发展可能有关。OBJECTIVE HIF-2α is a key protein of tumor in response to chronic hypoxia. The objective of this study was to investigate the expression of HIF- 2α in HCC cell line in hopoxia and investigate the expression and cilinical signifi- cance of HIF-2α in HCC. METHODS Western blot was used to detect the protein expression of HIF-2α in HCC cell lines in hypoxia. The study selected 66 patients confirmed by surgery and postoperative pathology in Shandong Provincial Qian foshan Hospital from 2013.01.01 to 2014.12.31. The expression of HIF -2α in hepatocellular carcinoma tissue and paired peritumoral tissue samples were investigated by immunohistoehemical staining and Western blot respectively. Stastistical analysis was used to ananlyze the correlation between the HIF- 2α protein and clinicopathological features. RESULTS The expression of HIF-2α was undetectable under normoxia while incubation of cells under hypoxia resuhed in significantly higher levels in HepG2 ,Bel-7402, Huh-7 and SMMC -7721. The expression level of HIF- 2α in the 12 cases of hepatocellu lar carcinoma tissues was higher than that in the paired peritumoral tissues（P〈0.01）. High expression of HIF-2α was found 65.2%（43/66） in tumor specimens,compared with 22.7%（15/66） in peritumoral tissues （P〈0.01）. The positive expression of HIF- 2α was significantly correlated with TNM stage（P=0. 033）. CONCLUSIONS There is high expression of HIF-2α protein in hepatocellular carcinoma tissues. It was significantly correlated with tumor TNM Stage. HIF-2α is in volved in the development and progression of HCC,and can be used as a potential therapeutic target.

关 键 词：HIF-2α 肝细胞癌 缺氧 临床意义 

分 类 号：R735.7[医药卫生—肿瘤]