Notch1、HIF-1和VEGF蛋白在非小细胞肺癌的表达及意义

Expression of Notchl, HIF-1 and VEGF in human non-small cell lung cancer and its significance

目的探讨Notch1、缺氧诱导因子-1（HIF-1）、血管内皮生长因子（VEGF）蛋白在非小细胞肺癌（NSCLC）组织的表达及其临床病理学意义。方法用免疫组化SP法分别检测65例NSCLC组织、15例正常支气管上皮组织中Notch1、HIF-1、VEGF蛋白的表达并分析它们与临床病理参数间的关系。结果Notch1、HIF-1、VEGF蛋白在非小细胞肺癌中阳性表达率分别为81.5%（53/65）、96.9%（63/65）、93.8%（61/65）,均明显高于正常支气管上皮组织阳性表达率的40%（6/15）、33.3%（5/15）、33.3%（5/15）（P〈0.05）;NSCLC中Notch1、HIF-1、VEGF蛋白的表达均与肿瘤临床分期和有无淋巴结转移等临床病理参数有关（P〈0.05）;Notch1、HIF-1与VEGF蛋白的表达三者两两间均呈显著正相关（r=0.332,0.428,0.505,P〈0.01）。结论Notch1、HIF-1、VEGF蛋白在NSCLC中均表达上调且互相相关,提示其在肺癌癌变发生、发展中可能起协同作用;肺癌细胞分泌的Notch1可能诱导HIF-1表达,HIF-1的高表达调节VEGF基因的表达从而促进新生血管形成和肿瘤侵袭转移。

Objective To determine the expressions of Notchl, HIF-1 and VEGF in human non-small cell lung cancer （NSCLC） and to explore its clinical pathological significance. Methods Immunohistochemical SP method was used to detect the expression of Notchl, HIF-1 and VEGF in 65 patients with NSCLC and 15 normal lung epithelium. The relationship among protein expression and clinic pathological parameters were analyzed. Results The positive rates of Notchl, HIF-1 and VEGF in NSCLC were 81.5% , 96. 9% and 93. 8% respectively, which were higher than that in normal lung epithelium （40%, 33.3% and 33.3% ） （ P 〈0. 05）. The positive expression level of Notchl, HIF-1 and VEGF were associated with tumor stage and lymph node metastasis （ P 〈0. 05）. There was a positive correlation between Notchl, HIF-1 and VEGF. Conclusion The enhanced expression of Notchl, HIF-1 and VEGF protein in NSCLC and their mutual relationship suggested that they may play a role and have synergic effect in the pathway of carcinogenesis and progression of NSCLC. The Notchl secreting from lung cancer cells may induce HIF-1 expression. The up-regulation of HIF-1 may promote the expression of VEGF gene expression, and VEGF can promote the formation of new tumor blood vessels and tumor invasion and metastasis.