A Study On The Correlation Between Expression Of E2f-1, Survivin Protein And Hpv Infection In Nsclc

【objective】1. To investigate the HPV 16, 18 infection in NSCLC and to elucidate the etiological role of HPV infection on the carcinogenesis of NSCLC;2. To study the relationship between HPV infection and expression of E2F-1,Survivin protein and to elucidate the possible molecular mechanisms that HPV infection induced carcinogenesis of NSCLC;3. To analyze the relationship between HPV infection,the expression of E2F-1 and Survivin protein and clinical pathological characteristics of NSCLC.【Methods】To collect and select 60 cases of the lung tissue with lesions surgically resected at Tongji Hospital affiliated to Tongji medical college of Huazhong University of Science and Technology, which included 47 NSCLC and 13 lung benign disease. Every case was divided into two groups: one was examined by PCR to detect the HPV DNA positive rate by HPV16E6, HPV18E7 type-specific primers; the other was made into neutral formalin-fixed paraffin sections and was detected the expression levels of E2F-1,Survivin protein in NSCLC and lung benign disease by immunohistochemical SP method. The experimental results were analyzed statistically.【Results】1. The results of detection of HPV16, 18-type DNA by PCRThe positive detection rate of HPV16,18 DNA in NSCLC 42.55%(20/47)was significantly higher than that in lung benign disease 7.69%(1/13). There was a significant difference between groups (P<0.05). 2.The expression levels of E2F-1,Survivin protein in NSCLC and lung benign disease detected by immunohistochemical SP methodExpression rate of E2F-1 protein in NSCLC 59.57%(28/47)was significantly higher than that in lung benign disease 23.08%(3/13), there was a significant difference between groups (P<0.05). Overexpression rate of E2F-1 was 64.29%(18/28)in NSCLC. Expression rate of Survivin protein was 61.70%(29/47)in NSCLC. There was no detectable expression of Survivin protein in lung benign disease.3. The expression correlation between E2F-1 protein and Survivin protein in NSCLCThe cases of positive expression of E2F-1,Survivin protein were 28 and 29 respectively in 47 cases of NSCLC. Both positive expression of the two proteins were 21 cases and both negative were 11 cases. Expression of the two proteins was positively correlated in NSCLC by correlation analysis of count data(χ2=5.183,p<0.05, r=0.3151).4. Expression of E2F-1,Survivin protein in HPV-positive and HPV-negative group in NSCLCExpression rate of E2F-1,Survivin protein were 85.00%(17/20),80.00%(16/20)respectively in HPV DNA positive group in NSCLC, which were both significantly higher than those in HPV DNA negative group 40.74%(11/27),48.15%(13/27).There was significant difference between groups (P<0.05).5. The relationship between HPV infection,expression of E2F-1,Survivin protein and clinical pathological characteristics of NSCLCNo correlation was found between HPV infection rate and age, sex, lymph node metastasis of patients, but there was significant correlation between HPV infection rate and history of smoking, histological type and degree of differentiation(P<0.05). HPV infection rate in smoking lung cancer patient 54.55% (18/33)was significantly higher than that in non-smokers14.29%(2/14)(P<0.05). There was higher positive rate of HPV in lung squamous cell carcinoma 55.17%(16/29)than lung adenocarcinoma 22.22%(4/18), the difference was significant(P<0.05). The positive rate of HPV in moderately differentiated NSCLC was significantly higher than that in highly and lowly differentiated NSCLC,there was a significant difference between groups(P<0.05).No correlation was found between expression rate of E2F-1 and age, sex, history of smoking, histological type, degree of differentiation and lymph node metastasis of patient(P﹥0.05).There was a significant relationship between expression of Survivin protein and lymph node metastasis(P <0.05). No correlation was found between expression of Survivin protein and age, sex, history of smoking, histological type and degree of differentiation of patient(P﹥0.05).【conclusion】1. Not only the detection rate of HPV16,18 DNA in NSCLC was significantly higher than that in lung benign disease, but also there was significant correlation between HPV infection rate and history of smoking, histological type and degree of differentiation. It suggested that HPV infection was associated with the development of NSCLC. It may be one of important etiology factors in carcinogenesis of NSCLC. Smoking may cooperate with HPV infection to promote carcinomatous change of lung.2. Most cases were positive expression of E2F-1,Survivin protein and correlated with HPV infection in NSCLC. As a result, HPV infection may promote the development of NSCLC by up-regulating expression of E2F-1,Survivin protein. This provides important reference for clinical developing new treatment of NSCLC, such as gene diagnosis, vaccine therapy, promoting apoptosis induced by E2F-1 independently of p53 pathway or blocking the expression and function of Survivin protein.