SENP-1和HIF-1α在肝细胞肝癌中的表达及临床意义

Expression of SENP-1 and HIF-1α in Hepatocellular Carcinoma and Its Clinical Significance

【目的】探讨SENP-1和HIF-1α在肝细胞肝癌组织,癌边缘组织及非癌组织中的表达与肝癌发展的关系和在肝癌新生血管生成中的作用。【方法】应用RT-PCR、荧光定量PCR和免疫组织化学方法检测57例肝癌组织,癌边缘组织,非癌组织中SENP-1和HIF-1α的表达,用CD34多克隆抗体标记新生血管内皮细胞,计数微血管密度(MVD),分析三者表达的相关性及与相关临床病理参数的关系。【结果】肝癌组织与癌边缘组织SENP-1、HIF-1αmRNA表达显著高于非癌组织,SENP-1和HIF-1α在癌边缘组织及癌组织细胞的胞浆内有明显表达,癌边缘组织的表达强度及阳性率显著高于癌组织(P<0.05),且表达阳性率随肝癌组织分化程度降低而增高,而在非癌组织的实质细胞中则不表达;在癌边缘组织及癌组织中SENP-1与HIF-1α蛋白表达正相关(r=0.761,P=0.000;r=0.346,P=0.008),HIF-1α蛋白表达与MVD负相关(r=-0.684,P=0.000;r=-0.808,P=0.000)。【结论】SENP-1和HIF-1α的表达可能是肝癌细胞适应缺氧微环境的重要调节机制,与肝癌新生血管生成密切相关。

[ Objective ] To investigate the expressions of SENP-1 and HIF-1α in hepatocellular carcinoma tissues, tumor- surrounding tissues, and non-cancer tissues, elucidate the correlations between SENP-1, HIF-1α and the occurrence of hepatocellular carcinoma and explore their roles in tumor angiogenesis. [ Methods ] The expressions of SENP-1 and HIF--1α in tumor tissues, tumor- surrounding tissues and non-cancer tissues were assessed by RT-PCR, quantitive PCR and immunohistochemistry in 57 cases with hepatocellular carcinoma. MVD was determined by anti-CD34 immunohistochemical staining, then we studied the relationship between the expressions and the clinicopathologic features. [ Results ] Compared with the non-cancer tissues, the mRNA levels of SENP-1 and HIF-1α in hepatocellular carcinoma tissues and tumor-surrounding tissues were much higher. There were positive expressions of SENP- 1 and HIF-1α in hepatocellular carcinoma tissues and tumor-surrounding tissues, and negative expressions in non-cancer tissues. The expressions of SENP-1 and HIF-1α in tumor-surrounding tissues were increased significantly compared with tumor tissues （P〈0.05）, and negative correlation with the differentiation degree of tumor tissues. There was positive correlation between the expressions of SENP-1 and HIF-1α in tumor and tumor-surrounding tissues （r = 0.761, P = 0.000; r = 0.346, P = 0.008）, while the expression of HIF-1α was negatively correlated with MVD （r = -0.684,P = 0.000; r = -0.808, P = 0.000）. [Conclusion] The expressions of SENP-1 and HIF-1α are an important regulation mechanism for hepatoma cells to adapt to hypoxia, and play an important role in hepatocellular carcinoma angiogenesis.