E2F1 overexpression associated with TS and survivin gene expressions in non-small cell lung cancer

Abstract

7669 Background: The thymidylate synthase (TS) expression is related to 5-FU sensitivity. The survivin expression is associated with tumor apoptosis, an indicator to predict the efficacy of chemotherapy. Recently, TS and Survivin have been reported to be E2F1 target genes. We investigate the clinical significance of the E2F1 gene expression in relation to gene expressions of TS and Survivin among non-small cell lung cancer (NSCLC). Methods: One hundred and twenty-seven NSCLC patients were investigated. Quantitative RT-PCR was performed to evaluate gene expressions of E2F1, TS, and survivin. The Ki-67 proliferation index and the apoptotic index using TUNEL method were also evaluated. Results: The E2F1 gene expression was significantly higher in stage II to III tumors than in stage I tumors (p=0.006). The E2F1 gene expression significantly correlated with the Ki-67 proliferation index (p<0.001), while no correlation was observed between the E2F1 gene expression and the apoptotic index. Regarding E2F1-target genes, the E2F1 gene expression significantly correlated with the TS gene expression (p<0.001). The E2F1 gene expression also significantly correlated with the survivin gene expression (p<0.001). The TS expression and the survivin expression significantly correlated with the Ki-67 proliferation index (p<0.001 and p<0.001, respectively). There was a significant inverse relationship between the survivin expression and the apoptotic index (p<0.001). The overall survival was significantly lower in patients with high-E2F1 tumors than in those with low-E2F1 tumors (p=0.002), especially among patients with stage II to III NSCLCs (p=0.018). The Cox regression analysis demonstrated that the E2F1 status was a significant prognostic factor for NSCLC patients (p=0.026). Conclusions: The present study revealed the E2F1 gene expression to correlate with TS and survivin gene expressions, and tumor proliferation. E2F1 overexpression could occur to produce more aggressive tumors with high proliferation rate and chemo-resistance during progression of NSCLCs. The suppression of E2F1 by RNA interference would be a useful strategy for cancer gene therapy. No significant financial relationships to disclose.