The Correlation Study Of E2F2 Induction On The Cell Proliferation Of Non-small Cell Cancer And Its Poor Prognosis

Non-small cell lung cancer(NSCLC) is one of the global incidence of malignant tumors, is also one of human cancer high mortality diseases with more than 1.2 million new cases each year. E2 F transcription regulatory factor involves in a wide range of biological processes, including cell cycle, cell apoptosis and DNA damage response. In our study, we examined whether E2F2 is related to NSCLC proliferation, prognosis and correlation between HPV infection, survivin protein expression and NSCLC was discussed. Methods:We used Western blot to detect the expression of E2F2 in fresh 86 NSCLC tumors and para-carcinoma tissues, and the correlation of E2F2 and cell proliferation, nvasion and metastasis and poor prognosis was analyzed. The expression of E2F2 protein and cellular localization in NSCLC was identified by immunohistochemistry. The E2F2 shRNA and scrambled shRNA were used for detecting the E2F2 expressionin in H1299、A549 cell lines, and the impacts of E2F2 expression on the proliferation and growth of cells were detected by MTT 、immunohistochemistry and colony formation experiments.The surgical lung tissues of 112 patientsconsist of 26 lung benign disease and 86 NSCLC. The whole cases were divided into two groups: one group was examined for the HPV DNA positive rate by PCR; the another group was performed neutral formalin-fixed paraffin sections fordetecting the expression levels of Survivin protein、E2F2 in NSCLC and lung benign disease by immunohistochemical. The experimental results were analyzed statistically. Results:Firstly, 86 NSCLC samples were analyzed by immunohistochemistry that E2F2 expression level was markedly increased by 62.8%(54/86) of all samples compared with those in the normal tissues.Further study showed that E2F2 expression was closely associated with clinical stage(P=0.039) and tumor size(P=0.045). Furthermore, Kaplan-Meier analysis indicated that high(Bad?)expression was significantly correlated to overall survival(P=0.045), but not to disease-free survival(P=0.288).In addition, our results showed that downregulating E2F2 expression could reduce cell viability and colony formation in NSCLC cells. The results in our study first revealed that E2F2 acts as an activator in tumor progress of NSCLC and could be very possible as a promising marker for the prognosis of patients with NSCLC.The expression of HPV16、18 DNA was in NSCLC by 43.00%(37/86)and in lung benign diseases by 7.69%(2/26). There was a significant difference between groups(P<0.05).Expression rate of E2F2 protein was in NSCLC by 62.80%(54/86)and in lung benign disease by 23.08%(6/26), there was a significant difference between groups(P<0.05). Over-expression rate of E2F2 wasin NSCLC by 64.81%(35/54). the expression Survivin protein wasin NSCLC by 61.63%(53/86),but there was no detectable expression of Survivin protein in the lung benign diseases.Expression rate of E2F2、Survivin protein showed 86.50%(32/37)、78.40%(29/37)respectively in HPV DNA positive group with NSCLC, which were both significantly higher than those in HPV DNA negative group by 38.8%(19/49)、49.0%(24/49)respectively.There was significant difference between groups(P<0.05). Conclusion:Our study suggests that E2F2 can be used as independent indicator of for overall survival in NSCLC patients. There is a correlation between E2F2 expression level and tumor size and clinical stage. E2F2 is also one of a promising markers for predicting the post-surgical poor prognosis of patients with NSCLC.E2F2 involved in NSCLC growth and proliferation. E2F2 high expression can promote the growth of cancer cells.HPV16, 18 DNA detection rates in NSCLC group are very high, and significantly higher than in control group with benign lung changes. Results suggest NSCLC has a correlation with HPV infection. HPV may be one the important cause resulting in occurrence of development of NSCLC.The expressions of E2F2 and Survivin in NSCLC have significant higher levels than those in control group, and are positively correlated with the expression of HPV. This can extrapolate that HPV may promote the NSCLC growth and proliferation by up-regulating expression of E2F2.This finding may provide a new key indicator for clinical treatment, and prognosis of patients with NSCLC.