E2F-1和survivin蛋白在非小细胞肺癌中的表达及其与HPV感染的相关性研究

Expression of E2F-1,survivin in non-small cell lung cancer and their relationship with HPV infection

背景与目的:人乳头状瘤病毒(human papillomavirus,HPV)与人类多种恶性肿瘤密切相关,而肺癌中亦有HPV的检出引起了众多学者的关注。本实验旨在研究非小细胞肺癌(non-small cell lung cancer,NSCLC)中高危HPV感染情况及其与E2F-1和survivin蛋白表达的关系,初步探讨HPV感染可能导致NSCLC发生、发展的分子机制。方法:特异型PCR检测47例NSCLC和13例肺良性病变组织中是否有HPV16、18DNA存在;免疫组化SP法检测E2F-1和survivin蛋白在肺病变组织中的表达。结果:NSCLC组HPV16、18DNA检出率为42.55%(20/47),明显高于肺良性病变组的7.69%(1/13,P<0.05)。NSCLC组中HPV的感染率与患者的吸烟史、组织学类型及分化程度有关(P<0.05),而与患者的年龄、性别及淋巴结转移无关(P>0.05)。NSCLC组中E2F-1蛋白表达阳性率为59.57%(28/47),其中64.29%(18/28)呈高表达,显著高于肺良性病变组23.08%(3/13,P<0.025)。NSCLC中survivin蛋白表达阳性率为61.70%(29/47),而肺良性病变组无表达。NSCLC组中E2F-1、survivin蛋白表达呈正相关(r=0.3151,P<0.05),且两者在HPV阳性组的阳性表达率分别为85.00%(17/20)和80.00%(16/20),均显著高于HPV阴性组的40.74%(11/27)和48.15%(13/27),差异均有统计学意义(P<0.05)。结论:HPV16、18感染在NSCLC的发生中可能有病因学意义,其致癌机制可能与E2F-1和survivin蛋白表达上调有关。

Background and purpose：Research has showed that HPV is closely related with many malignant tumors including lung cancer.This study aimed to investigate HPV 16 and 18 infections,the expression of E2F-1 and survivin protein in NSCLC as well as the correlation among them,and to elucidate the possible molecular mechanisms that HPV infection induced carcinogenesis of NSCLC.Methods：Forty-seven NSCLC cases and 13 benign lung cases were examined by type-specific PCR for the purpose of detecting HPV DNA positive rate and by IHC for the expression level of E2F-1 and survivin protein,respectively.Results：The positive rates of HPV16 and 18 DNA in NSCLC was 42.55%（20/47） and were significantly higher than that in benign lung cases（7.69%,1/13）（P〈0.05）.No correlation was found between HPV infection,age,sex and lymph node metastasis,but there was a significant correlation between HPV infection rate and patients with a history of smoking,histological type and degree of differentiation of patients with NSCLC（P〈0.05）.Expression rate of E2F-1 protein in NSCLC was 59.57%（28/47） and was significantly higher than that in benign lung cases（23.08%,3/13）（P〈0.025）.Overexpression rate of E2F-1 was 64.29%（18/28） in NSCLC.Expression rate of survivin protein was 61.70%（29/47） in NSCLC but there was no expression in the benign lung cases.Expression of the two proteins was positively correlated in NSCLC（r=0.3151,P〈0.05）.Expression rate of E2F-1and survivin protein were 85.00%（17/20） and 80.00%（16/20）,respectively,in HPV DNA positive group,compared to 40.74%（11/27） and 48.15%（13/27） in HPV DNA negative groups,there was significant difference between the groups（P〈0.05）.Conclusion：HPV16 and 18 infections may have etiologic significance for NSCLC;the possible mechanisms may be associated with the up-regulated expression of E2F-1 and survivin protein.