乏氧诱导因子-1α与肝细胞癌患者预后生存相关性分析  

HIF-1αis a negative prognostic indicator associated with poor survival benefits of HCC patients

作　　者：周林 汪京[1] 赵阳 李瀚[1] 杜国盛 史宪杰[2] 贺强[1] 郎韧[1] Zhou Lin;Wang Jing;Zhao Yang;Li Han;Du Guosheng;Shi Xianjie;He Qiang;Lang Ren(Department of Hepatobiliary and Pancreaticosplenic Surgery,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China;Faculty of Hepato-Pancreato-Biliary Surgery,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]首都医科大学附属北京朝阳医院肝胆胰脾外科,北京100020 [2]解放军总医院肝胆胰医学部,北京100051

出　　处：《肝癌电子杂志》2021年第3期17-25,共9页Electronic Journal of Liver Tumor

基　　金：北京市自然科学基金(7212042);首都医科大学校自然基金(PYZ20014)。

摘　　要：目的:探讨乏氧诱导因子-1α(hypoxia-inducible factor 1-alpha,HIF-1α)对肝细胞癌患者预后生存的影响。方法:回顾性分析了136例2016年1月至2017年6月在解放军总医院接受肝切除术的患者病例信息。同时以免疫组织化学(immunohistochemistry,IHC)染色检测癌及癌旁组织中HIF-1α、p-Akt、p-mTOR、PTEN与p27,以及糖酵解中LDHA、GLUT-1、VEGF蛋白的表达,分析与肿瘤分化程度的相关性,探讨HIF-1α在肝细胞癌发生中的作用机制;对两组患者的预后生存进行单因素预后分析,以Cox回归模型分析影响肝细胞癌患者预后生存的危险因素。结果:HIF-1α、VEGF、GLUT1、LDHA、p-Akt和p-mTOR在低分化肝细胞肝癌和癌组织中高表达;HIF-1α分别与VEGF、GLUT1、LDHA、p-Akt和p-mTOR呈正相关。同时,高-中分化肝细胞癌患者较低分化肝细胞癌患者有更好的生存优势。Cox回归分析显示,肿瘤分化程度、HIF-1α和Ki-67是影响预后的独立危险因素。结论:HIF-1α是肝细胞癌预后的独立危险因素,低分化肝细胞癌同时伴有HIF-1α高表达和高Ki-67提示预后生存更差。Objective:To explore the survival benefits of hypoxia-inducible factor-1α(HIF-1α)inpatients with hepatocellular carcinoma(HCC).Methods:We enrolled 136 patients who performed liver resection.Liver tissue were collected to analyze the expression of HIF-1αand others with immunohistochemistry(IHC).Mean integral optical density(MIOD)of tissue IHC was used to measure the expression level of different differentiated tumors.Survival rates were calculated using the Kaplan-Meier method and evaluated with the log-rank test.Cox proportional model was used to analyze the independent risk factors affecting the survival time.Results:HIF-1α,VEGF,GLUT1,LDHA,p-Akt and p-mTOR were highly expressed in poorly differentiated HCC and carcinoma tissue.HIF-1αwas positive associated with VEGF,GLUT1,LDHA,p-Akt and p-mTOR,respectively.Meanwhile,high-middle differentiated HCC patients suggested a well survival benefits over that low differentiated HCC patients.Cox regression analysis indicated that tumor differentiation,HIF-1αand Ki-67 were the prognostic independent risk factors.Conclusion:HIF-1αis an independent risk factor for prognosis of HCC.Low differentiated HCC with high HIF-1αexpression and high Ki-67displayed a poor prognostic survival.

关 键 词：乏氧诱导因子-1Α 肝细胞癌 瓦伯格效应 糖代谢 预后生存分析 

分 类 号：R735.7[医药卫生—肿瘤]