缺氧诱导因子2α在肝癌中的表达及其与血管生成、上皮间质转化的关系

Expression of hypoxia-inducible factor-2α in hepatocellular carcinoma and its relationship with epithelial-mesenchymal transition and angiogenesis

目的研究缺氧诱导因子2α(HIF-2α)在肝细胞肝癌中的表达情况及其与血管生成和上皮间质转化(EMT)的关系。方法收集正常肝组织15例、肝癌组织和相应的癌旁组织各63例,采用免疫组化染色法检测HIF-2α的表达,分析其表达与肝癌临床病理特征及生存预后之间的关系;同时分析肝癌组织中HIF-2α、白细胞分化抗原34(CD34)、波形蛋白(Vimentin)的表达,探究HIF-2α的表达与血管生成、EMT的关系。结果免疫组化染色法显示HIF-2α在肝癌组织中主要在胞质表达,显著高于癌旁组织及正常肝组织(P<0.001)。HIF-2α的表达与肿瘤最大径、肿瘤TNM分期、Edmondson分级及包膜和血管侵犯有关,与患者年龄、性别、乙肝表面抗原表达、甲胎蛋白(AFP)、Child-Pugh分级、肿瘤结节数目及肿瘤内坏死无关。相关性分析显示HIF-2α的表达与微血管密度(MVD)有关(t=5.919,P<0.001),与Vimentin的表达无关(r=1.013,P=0.209)。生存分析显示,高表达组术后总体生存率明显低于低表达组(P<0.001)。多因素分析显示瘤内坏死、肿瘤血管侵袭和HIF-2α表达是影响肝癌患者总生存率的独立危险因素。结论HIF-2α可促进肝癌血管生成,但可能不参与EMT,可作为判断肝癌患者预后的指标之一。

Objective To explore the expression of hypoxia-inducible factor-2α （ HIF-2α） in hepatocellular carci-noma and the relationship with epithelial-mesenchymal transition（EMT）and angiogenesis. Methods The expres-sions of HIF-2αin 63 cases of hepatocellular carcinoma tumor tissues and 15 normal liver tissues were examined by immunohistochemistry. To assess the relationship between the expressions of HIF-2α, EMT and angiogenesis,the expressions of CD34 and Vimentin were detected in hepatocellular carcinoma. Results Immunohistochemistry showed that HIF-2α mainly expressed in the cytoplasm, the rate of HIF-2α overexpression in hepatocellular carci-noma tissues was significantly higher than the other two groups （ P〈0. 001 ） . The expression of HIF-2αwas correla-ted with tumor size,TNM stages,Edmondson grade, capsule or vascular invasion. HIF-2α expression had a signifi-cantly positive correlation with microvascular density （ t=5. 919 , P〈0. 001 ） , but not vimentin （ r=1. 013 , P=0. 209 ） . Survival analysis showed that the prognosis was poor in patients with HIF-2αoverexpression （ P〈0. 001 ） . Cox regression demonstrated that the expression of HIF-2α,tumor necrosis and vascular invasion were the independ-ent risk factors for cumulative survival in hepatocellular carcinoma patients. Conclusion HIF-2α can promote an-giogenesis, but may not participate in EMT. It may be a potential tumor marker for prognosis of hepatocellular car-cinoma.