缺氧诱导因子-1α和缺氧诱导因子-2α在人非小细胞肺癌表达的比较  

Expression of HIF-1α and HIF-2α in non-small cell lung cancer

作　　者：袁凯[1] 钱成[2] 

机构地区：[1]南京医科大学附属常州第二人民医院胸心外科,江苏常州213003 [2]复旦大学附属中山医院胸外科

出　　处：《中华实验外科杂志》2010年第5期614-616,共3页Chinese Journal of Experimental Surgery

摘　　要：目的观察缺氧诱导因子（HIF）-1α和HIF-2α在人非小细胞肺癌（NSCLC）中的表达并探讨其临床意义。方法采用实时定量聚合酶链反应（PCR）和Westernblot法检测不同缺氧时程HIF-1α和HIF-2α的mRNA和蛋白表达，比较两者差异。进一步运用免疫组织化学技术检测两者在140例NSCLC患者标本中的表达，结合相关临床病理因素探讨其临床意义。结果在缺氧条件下，HIF-1α蛋白在4h即迅速升至峰值，之后快速下降，而HIF-2α蛋白则表现为逐步上调并持续维持在较高表达水平。在140例NSCLC的标本研究中，HIF-2α与肿瘤大小、淋巴结转移和TNM分期关系密切（P〈0．05），并且是预后的不良因素（P〈0．05）。结论HIF-2α可能是肿瘤适应乏氧环境的主要调节因子，相较于HIF-1α、HIF-2α在NSCLC的靶向治疗研究中更具有价值。Objective To study the expression patterns and significance of hypoxia inducible factor （HIF）-1α and HIF-2αin non-small cell lung cancer （NSCLC）. Methods The expression levels of HIF-1α and HIF-2α mRNA and protein were detected by quantiteve real-time reverse transcription-poly- merase chain reaction （RT-PCR） and Western blotting respectively when exposed to hypoxia （0.5% O2 ） for various durations and the difference was compared. The expression of HIF-1αand HIF-2α protein in 140 surgically resected NSCLC samples was assessed by using immunohistochemistry, and its correlation with clinicopathology was explored. Results HIF-1α protein was transiently increased and reached a peak at 4 h and then decreased almost to at basal line 12 h later when the A549 cells were cultured under hypoxia, while HIF-2α protein was gradually up-regulated and persisted at a high level after a long-term hypoxia exposure. In 140 NSCLC samples, a significant correlation （P 〈 0.05） was noticed between the expression of HIF-2α and the tumor size,lymph node metastasis and the TNM stage （P 〈 0. 05）. Tumor HIF-2α expression was also found as a statistically significant adverse prognostic factor in terms of the overall survival （P 〈 0.05）. Conclusion Taken together, it conclude that HIF-2α may play a dominant role in the process of tumor response to hypoxia, which suggests that it may be of more obvious value in therapeutic target research for NSCLC.

关 键 词：肺癌 缺氧诱导因子 免疫组织化学 

分 类 号：R734.2[医药卫生—肿瘤]