乏氧诱导因子-1α与肝细胞癌患者预后生存相关性分析

摘要/Abstract

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。

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

Abstract: 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-1α and 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-1α was 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-1α and Ki-67 were the prognostic independent risk factors. Conclusion: HIF-1α is an independent risk factor for prognosis of HCC.Low differentiated HCC with high HIF-1α expression and high Ki-67displayed a poor prognostic survival.

Key words: Hypoxia-inducible factor-1α, Hepatocellular carcinoma, Warburg effect, Glucose metabolism, Prognosis

周林, 汪京, 赵阳, 李瀚, 杜国盛, 史宪杰, 贺强, 郎韧. 乏氧诱导因子-1α与肝细胞癌患者预后生存相关性分析[J]. 肝癌电子杂志, 2021, 8(3): 17-25.

Zhou Lin, Wang Jing, Zhao Yang, Li Han, Du Guosheng, Shi Xianjie, He Qiang, Lang Ren. HIF-1α is a negative prognostic indicator associated with poor survival benefits of HCC patients[J]. Electronic Journal of Liver Tumor, 2021, 8(3): 17-25.

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