缺氧诱导因子-1α蛋白在肝癌组织中的表达及临床意义

目的 检测肝癌及癌旁组织中缺氧诱导因子-1 α(HIF-1 α)基因蛋白的表达及临床意义。方法 用免疫组织化学、western blot和RT—PCR技术检测35例肝细胞癌、26例肝硬化组织及15例正常肝组织中HIF-1 α蛋白和基因的表达情况,并分析其与临床病理特点之间的关系。 结果 免疫组织化学显示HIF-1α蛋白在肝硬化和肝癌组织中普遍表达,在肝硬化组织中的表达明显高于正常肝脏组织中的表达;但肝癌组织中因大片状坏死后伴大量纤维结缔组织增生的肝细胞条索中HIF-1 α蛋白的表达强度高于肝硬化组织,肝硬化组织HIF-1α蛋白的表达强度明显高于肝癌组织(54％与31％,x2=4.09,P<0.05);westernblot和RT-PCR结果与免疫组化结果相似。HIF-1α蛋白在肝癌组织中的表达强度与分化程度有关(x2=4.64,P<0.05),与有无肝内外转移有关(x2=7.15,P<0.05);但HIF-1α的表达与门静脉有无癌栓、预后及HBsAg表达无关。 结论 HIF-1 α蛋白在肝癌和肝硬化组织中普遍表达,且只受缺氧因素的影响,与肿瘤的分化程度和肝癌的转移有关,但与有无门静脉癌栓、HBsAg表达及预后无关,为肝癌的治疗提供新的思路。

Expression and clinical significance of HIF-1 α protein in hepatocellular carcinoma tissues

OBJECTIVE: To investigate the expression and clinical significance of HIF-1a protein in hepatocellular carcinoma (HCC) tissues. METHODS: Immunohistochemistry (IHC), Western blotting and RT-PCR techniques were used to detect the expression of the HIF-1a gene protein in 35 HCC, 26 cirrhotic and 15 normal liver tissues. Their relationship with the pathological characteristics of the tumors were also analyzed. RESULTS: The positive rates of HIF-1a expression in HCC tissues was 94%, which was similar to the positive rates of HIF-1a expression in liver cirrhosis tissues of 92%, but was higher than that in normal hepatic tissues of 7%, but the residual proliferatic hepatic trabeculae among the necrotic liver cells and the fibrotic tissues expressed HIF-1a strongly in comparison with the cirrhotic liver tissues. The expression intensity of HIF-1a protein of the cirrhotic liver tissues was stronger than that in HCC; the results by Western blotting and RT-PCR were in accordance to that by IHC. In addition, the expression intensity in HCC had a negative correlation in differentiation degree and a positive correlation to intrahepatic and extrahepatic metastases but no correlation was found between HIF-1a expression and the existence of portal vein tumor emboli, prognosis and the status of HBsAg. CONCLUSION: HIF-1 protein was expressed in HCC and cirrhotic liver tissues, and was only affected by the factor of hypoxia. The expression of HIF-1a protein is associated with the differentiation of the tumor and its intrahepatic and extrahepatic metastases but was not related to the existence of portal vein tumor emboli, prognosis and the status of HBsAg. This phenomenon may provide a new idea for the treatment of liver cancer.