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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 investigate the expression of hypoxia inducible factor 2α (HIF-2α) in hepatocellular carcinoma and its relationship with angiogenesis and epithelial-mesenchymal transition (EMT). Methods Fifteen cases of normal liver tissue and 63 cases of corresponding liver cancer tissues and adjacent tissues were collected. The expression of HIF-2α was detected by immunohistochemistry and the relationship between the expression of HIF-2α and clinicopathological features and prognosis of HCC was analyzed. Meanwhile, To analyze the expression of HIF-2α, CD34 and Vimentin in hepatocellular carcinoma and to investigate the relationship between HIF-2α expression and angiogenesis and EMT. Results Immunohistochemical staining showed that HIF-2α was mainly expressed in the cytoplasm of hepatocellular carcinoma, which was significantly higher than that in paracancerous tissues and normal liver tissues (P <0.001). The expression of HIF-2α correlated with the maximum diameter of tumor, TNM stage of tumor, Edmondson classification and invasion of blood vessel, and the age, gender, hepatitis B surface antigen expression, AFP, Child-Pugh classification, The number and tumor necrosis has nothing to do. Correlation analysis showed that the expression of HIF-2α was correlated with the microvessel density (MVD) (t = 5.919, P <0.001), but not with Vimentin (r = 1.013, P = 0.209). Survival analysis showed that the overall survival rate of the high expression group was significantly lower than that of the low expression group (P <0.001). Multivariate analysis showed that tumor necrosis, tumor vessel invasion and HIF-2αexpression were independent risk factors affecting the overall survival rate of patients with HCC. Conclusions HIF-2α can promote the angiogenesis of hepatocellular carcinoma, but may not participate in EMT, which may be used as an index to judge the prognosis of hepatocellular carcinoma.