低氧诱导因子-2α在肝细胞癌中的表达及其临床意义

王秀超; 苑占娜; 李莎莎; 盛俊; 赵天锁; 高松; 任贺; 黄鹤; 郝继辉

doi:10.3969/j.issn.1000-8179.2011.10.006

摘要: 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HIF-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。

Abstract: Expression of Hypoxia-Inducible Factor-2α in Hepatocellular Carcinoma and Its ClinicalSignificanceXiuchaoWANG1, Zhanna YUAN1, Shasha LI1, Jun SHENG1, Tiansuo ZHAO1, Song GAO1, He REN1, He HUANG2, Jihui HAO1Correspondence to: Jihui HAO, E-mail: jihuihao@yahoo.comDepartment of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute andHospital, Tianjin 300060, ChinaSchool of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, ChinaThis work was supported by grants from the National Natural Science Foundation of China (Grant no. 30901448) and the Natural Sci-ence Foundation of Tianjin (Grant no. 09JCZDJC17100)Abstract Objective: To investigate HIF-2α expression in hepatocellular carcinoma ( HCC ), and to explore its correlation withclinical 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 withSPSS13.0 software. Results: There was no HIF-2α expression in normal liver tissue; however, 32 patients were grade ( - ), 32 patientswere grade ( + ), and 40 patients were grade ( ++ ) with HIF-2α–positive specimens. The HIF-2α expression in the HCC tissue was evi-dently correlated with tumor differentiation, TNM stage, and paraneoplastic liver cirrhosis ( P < 0.05 ). There was a positive correlationbetween HIF-2α and MVD ( P < 0.05 ). The three-year overall survival rate was significantly lower among patients with higher HIF-2αexpression than those with lower HIF-2α expression ( 12.8% vs. 60.8%, P < 0.001 ). HIF-2α is an independent prognostic factor for he-patocellular carcinoma in Cox multivariate analysis ( P < 0.001 ). Conclusion: The expression of HIF-2α is correlated to patients' sur-vival, differentiation of tumor, tumor stage, and angiogenesis of hepatocellular carcinoma. The expression of HIF-2α may be considereda reference criterion for evaluating the progression, metastasis, and prognosis of HCC.Keywords Hepatocellular carcinoma ( HCC ); Hypoxia-inducible factor-2α ( HIF-2α ); Microvessel density ( MVD );Immunohistochemistry; Prognosis