【摘要】 目的:探讨胶质瘤相关癌基因同源蛋白-1(Gli-1)及上皮-间质转化(epithelial-mesenchymal transition,EMT)相关蛋白Snail、E-cadherin及N-cadherin在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及临床意义。方法:采用免疫组织化学法检测天津市胸科医院2010年1月至2012年2月经手术切除送检的67例NSCLC组织及20例正常肺组织中Gli-1、Snail、E-cadherin及N-cadherin蛋白的表达情况,分析其与患者临床病理特征及预后的关系;采用逆转录多聚酶链反应(RT-PCR)法测定Gli-1、Snail、E-cadherin及N-cadherin基因在20例NSCLC及其对应癌旁正常肺组织中m RNA的表达情况。结果:1)Gli-1、Snail、E-cadherin及N-cadherin在NSCLC组织中的阳性表达率分别为61.19%(41/67)、50.75%(34/67)、56.72%(38/67)、53.73%(36/67),在正常肺组织中的阳性表达率为20%(4/20)、10%(2/20)、100%(20/20)、5%(1/20),表达差异具有统计学意义(P<0.05);2)患者癌组织中Gli-1高表达与淋巴结转移、分化程度和临床分期密切相关(P<0.05),与性别、年龄、肿物大小和病理分型无相关性;Gli-1的表达与E-cadherin的表达呈负相关(r=-0.325,P<0.05),与Snail、N-cadherin的表达呈正相关(r=0.379、r=0.490,P<0.05);3)RT-PCR结果显示,Gli-1、Snail和N-cadherin m RNA的表达量高于正常余肺组织(P<0.05),E-cadherin m RNA的表达量低于正常余肺组织(P<0.05);4)Gli-1、Snail和N-cadherin高表达的患者表现出更差的预后和更低的生存率(P<0.05),E-cadherin阴性组的患者较阳性组患者显示出更差的预后和更低的生存率,差异具有统计学意义(P<0.05),Cox比例风险回归模型分析结果显示,E-cadherin阴性、淋巴结转移、临床分期、分化程度是影响NSCLC患者预后的独立危险因素。结论:在NSCLC中,Hedgehog信号通路的异常活化与EMT存在密切相关性,Gli-1与EMT相关蛋白的表达对判断NSCLC患者的临床特征及预后具有一定提示作用。更多还原

【Abstract】 Objective: To investigate the expression and clinical significance of glioma cancer-related gene homologous protein 1(Gli-1)and epithelial-mesenchymal transition(EMT)-related proteins,namely,Snail,E-cadherin,and N-cadherin in non-small cell lung cancer(NSCLC).Methods: Immunohistochemical staining was performed to determine the expression levels of Gli-1,Snail,E-cadherin,and Ncadherin in 67 cases of NSCLC and 20 cases of normal lung tissues and its relationship with clinicopathological features and prognosis was explored.Another 20 samples of fresh NSCLC tissues and corresponding normal lung tissues were collected to detect the m RNA level through reverse transcription polymerase chain reaction(RT-PCR).Results: 1) The positive rates of Gli-1,Snail,E-cadherin,and Ncadherin in NSCLC were 61.19%(41/67),50.75%(34/67),56.72%(38/67),and 53.73%(36/67),respectively; whereas those of normal lung tissues were 20%(4/20),10%(2/20),100%(20/20),and 5%(1/20),respectively.These two sets of data have significant statistical difference(P<0.05).2) The high expression of Gli-1 in tumor tissues was closely related to lymph node metastasis,tumor,node,and metastasis(TNM) stage,and tumor differentiation(P<0.05) but was not associated with gender,age,tumor size,and pathological type.The expression of Gli-1 in NSCLC tissues was negatively correlated with E-cadherin(r=-0.325,P<0.05) and positively correlated with Snail and N-cadherin(r=0.379,r=0.490,P<0.05).3) RT-PCR results showed that the expression levels of Gli-1,Snail,and N-cadherin m RNA were significantly higher in NSCLC cases than in normal lung cases(P<0.05).The expression level of E-cadherin m RNA was lower in tumor tissues than in lung tissues(P<0.05).4) Patients with high expression levels of Gli-1,Snail,and N-cadherin had significantly worse prognosis and lower survival rate than those with low expression(all P<0.05),whereas patients with low expression levels of E-cadherin had significantly better prognosis and lower survival rate than those with high expression(P<0.05).Multivariate Cox’s proportional hazard regression analysis indicated that E-cadherin-negative group expression,lymph node metastasis,TNM stage,and tumor differentiation were independent prognostic factors for NSCLC.Conclusion: The abnormal activation of Hedgehog signaling pathway in NSCLC is correlated with EMT.Detecting the expression levels of Gli-1 and EMT-related proteins Snail,E-cadherin,and Ncadherin might be helpful in understanding the clinicopathological features and prognosis of patients with NSCLC.更多还原