非小细胞肺癌中NDRG1与HIF-1α表达模式及相关性的研究

Expression and association of NDRG1 with HIF-1α in non-small cell lung cancer

目的探讨非小细胞肺癌组织中NDRG1(N-myc下游调节因子1)与HIF-1α(缺氧诱导因子1α)的表达模式及关联。方法应用免疫组织化学方法检测105例非小细胞肺癌及癌旁肺组织中NDRG1和HIF-1α的蛋白表达。应用Western Blotting检测12对新鲜肺癌组织及癌旁肺组织中NDRG1及HIF-1α的蛋白表达。结果 NDRG1与HIF-1α在非小细胞肺癌组织中具有相似的表达模式,均主要表达于细胞浆,阳性率分别为55.2%(58/105)及50.5%(53/105),部分病例伴有细胞核(分别为20.0%(21/105)及35.2%(37/105))和细胞膜(分别为11.4%(12/105)及7.6%(8/105))的表达,总的阳性率分别为60.0%(63/105)及53.3%(56/105)。NDRG1在癌旁肺组织中的表达(17.1%(18/105))低于癌组织(<0.05),HIF-1α在癌旁肺组织中的表达(46.7%(49/105))与癌组织中的表达无显著差异(>0.05),NDRG1与HIF-1α在非小细胞肺癌组织中的表达水平呈正相关(r=0.210,<0.05)。Western Blotting结果显示NDRG1在肺癌组织中的表达高于癌旁肺组织(<0.05),其在癌组织中的表达与HIF-1α的蛋白表达呈正相关(<0.05)。HIF-1α在癌及癌旁组织中的表达无明显差异(<0.05)。结论 NDRG1在非小细胞肺癌高表达与HIF-1α表达呈正相关,二者可能在肿瘤内部缺氧诱导的应激反应过程中存在相互作用。

Objective To investigate the expression types of N-myc downstream regalator（NDRG1） and hypoxia induciug factor-1α（HIF-1α） in non-small cell lung cancer（NSCLC） tissues and their association.Methods We examined the protein expression of NDRG1 and HIF-1α in NSCLC and paired adjacent lung tissues using immunohistochemistry（IHC）and Western Blotting.Results NDRG1 and HIF-1αexpression was similar in types in NSCLC with staining mainly in cytoplasm（positive rate was 55.2%（58/105）and 50.5%（53/105） respectively）.Cytomembrane（positive rate was 11.4%（12/105） and 7.6%（8/105） respectively） and nuclear staining（positive rate was 20.0%（21/105） and 35.2%（37/105） respectively） was also seen in some cases.The total positive rates were 60.0%（63/105） and 53.3%（56/105） respectively.NDRG1 expression in paired lung tissues（17.1%（18/105）） was lower than that in cancer tissues（0.05）,with no significant difference for HIF-1α expression level in paired lung tissues（46.7%（49/105）） and cancer tissues（0.05）.There was a positive correlation between expressions of NDRG1 and HIF-1α in NSCLC（r=0.210,0.05）.Western Blotting showed an increased expression of NDRG1 in NSCLC tissues compared to normal lung tissues（0.05）.NDRG1 expression in NSCLC tissues was positively associated with HIF-1α（0.05）,but with no significant difference for HIF-1α expression in NSCLC tissues and normal lung tissues（0.05）.Conclusion The present findings indicate an upregulation of NDRG1 expression in NSCLC tissues which was positively associated with HIF-1α expression and a possible interaction between the two proteins in the cancer tissues during stress respons against hypoxia.