肝癌组织缺氧诱导因子-1α的动态表达特征及其临床价值

Expression characteristics of hypoxia inducible factor-1α and its clinical values in hepatocellular carcinoma

目的 探讨缺氧诱导因子-1α（HIF-1α）及转录异常对肝癌的临床价值.方法 以肝癌模型观察肝病理学、HIF-1α转录及表达水平的动态变化;以自身配对法收集手术切除的肝癌和癌周组织,抽提总RNA并扩增分析HIF-1α mRNA表达;以免疫组织化学和Western blot分析HIF-1α表达、胞内分布及临床病理学特征.根据不同资料采用方差分析、确切概率法、Pearson或Spearman等级相关分析进行统计学分析. 结果癌变过程中肝HIF-1α仅和HIF-1αmRNA均呈梯度表达.在对照组、变性组、癌前组和癌变组中,肝HIF-1α阳性率为0、77.8%、88.90/o和100%;HIF-1α/β-肌动蛋白比值为0.16±0.02、0.29±0.04、0.52±0.03和0.84±0.02,均显著高于对照组（P=0.000）.人肝癌组织HIF-1α阳性率为80.0%（28/35）,癌旁为100%（35/35）,且与瘤体大小呈正相关,与分化程度呈负相关,与肿瘤数目及HBsAg阳性无关.结论 HIF-1表达与肝癌发生、发展相关,是肝癌治疗的分子靶目标.

Objective To investigate the dynamic expression of hypoxia inducible factor-1α（HIF1α） and its clinical values in hepotacellular carcinoma（HCC）.Methods The dynamic changes of liver pathology,HIF-1α transcription and expression were observed through the hepatoma model.The self-control specimens from 35 human HCC patients were collected and the expression,cellular distribution,and clinopathological features of HIF-1α and its gene was analyzed by immohistochemistry,western blotting and nested-PCR,respectively.Results Both levels of hepatic HIF-1α and HIF-1α mRNA expression increased during the HCC development course.The incidence of HIF-1α and the ratio of HIF-1α to β-actin was 0% and 0.16±0.02 in the control rats,77.8% and 0.29±0.04 in the denatured rats,88.9% and 0.52±0.03 in the precancerous rats,and 100% and 0.84±0.02 in the cancerous rats respectively,with significant difference between the control group and any of the experimental groups（P=0.000）.The positive HIF-1α was brown and granule-like and mainly presented in cytoplasm and few in nucleus.The incidence of HIF-1α was 80%（28/35）in HCC and 100%（35/35）in its surrounding tissues.The clinical pathological features indicated HIF-1α expression associated with tumor size and differentiation degree the of HCC.No correlation was found between HIF-1 α and tumor numbers or positive-Hbsag.Conclusions HIF-1α expression is associated with occurrence and development of HCC,and is perpahps a target molecule for HCC therapy.