低氧诱导因子-2α在肝细胞癌中的表达及其临床意义

Expression of Hypoxia-Inducible Factor-2ɑ in Hepatocellular Carcinoma and Its Clinical Significance

目的:分析低氧诱导因子-2α(HIF-2α)在肝细胞癌组织中的表达,探讨其与肝细胞癌临床病理特征的相关性及临床意义。方法:收集天津医科大学附属肿瘤医院104例经手术治疗并有完整随访资料的肝细胞癌和10例正常肝组织标本,用免疫组化方法观察HIF-2α和CD34在癌组织中的表达情况,分析HIF-2α表达水平与肝细胞癌微血管密度、临床病理特征及患者预后的关系。结果:正常肝组织无HlF-2α表达,104例患者中HIF-2α蛋白表达(-)32例,(+)32例,(++)40例;HIF-2α表达与肝细胞癌的分化程度、TNM分期及伴发肝硬化呈正相关关系(P<0.05);HIF-2α蛋白较高表达组MVD显著高于HIF-2α蛋白较低表达组(P<0.05);HIF-2α高表达患者组的3年生存率低于低表达患者组(12.8%vs 60.8%,P<0.001)。经Cox多因素回归分析,HIF-2α是肝细胞癌的独立预后因素(P<0.001)。结论:HIF-2α的阳性表达与肝细胞癌血管新生、病理分级、TNM分期及总生存率密切相关;提示HIF-2α可作为评估肝细胞癌进展及预后的指标之一。

Objective： To investigate HIF-2α expression in hepatocellular carcinoma （ HCC ）, and to explore its correlation with clinical features of HCC. Methods： A total of 104 HCC resection samples with complete clinical and prognostic data were collected. The expression of HIF-2α and CD34 in 104 specimens of HCC and 10 normal liver tissues were detected by SP immunohistochemistry. The correlation of HIF-2α to the microvascular density （ MVD ）, clinicopathologic features, and prognosis of HCC were analyzed with SPSSI3.0 software. Results： There was no HIF-2α expression in normal liver tissue; however, 32 patients were grade （ - ）, 32 patients were grade （ ＋ ）, and 40 patients were grade （ ＋＋ ） with HIF-2α - positive specimens. The HIF-2α expression in the HCC tissue was evidently correlated with tumor differentiation, TNM stage, and paraneoplastic liver cirrhosis （ P 〈 0.05 ）. There was a positive correlation between HIF-2α and MVD （ P 〈 0.05 ）. The three-year overall survival rate was significantly lower among patients with higher HIF-2α expression than those with lower HIF-2α expression （ 12.8% vs, 60.8%, P 〈 0.001 ）. HIF-2α is an independent prognostic factor for hepatocellular carcinoma in Cox multivariate analysis （ P 〈 0.001 ）. Conclusion： The expression of HIF-2α is correlated to patients＇ survival, differentiation of tumor, tumor stage, and angiogenesis of hepatocellular carcinoma. The expression of HIF-2α may be considered a reference criterion for evaluating the progression, metastasis, and prognosis of HCC.