Prognostic impact of Raf-1 and p-Raf-1 expressions for poor survival rate in non-small cell lung cancer

Overexpression of Raf-1 has commonly been observed in solid tumors including non-small cell lung cancer (NSCLC). The objective of this study was to investigate whether overexpression of Raf-1, phosphorylated-Raf-1 (p-Raf-1) or both correlates with poor survival rate in NSCLC patients and to explore associations between expression of these proteins and NSCLC cell fate both in vitro and in vivo. Expression of Raf-1 and p-Raf-1 were detected by immunohistochemistry in tumor specimens from 152 NSCLC patients and associations between their expression and the clinicopathological characteristics were assessed. Five-year median survival rate of patients were analyzed by Kaplan-Meier method, log-rank test and Cox regression. Cell fate was compared between normal tumor cells and those with Raf-1 silencing, in both the adenocarcinoma cell line A549 and xenografted mice that were infected with the A549 cell line. The incidence of overexpression of both Raf-1 and p-Raf-1 in NSCLC was much higher than normal control (P < 0.05), and the survival rate of patients with positive expression of Raf-1, p-Raf-1 or both was found to be significantly lower than the negative group (P < 0.05). Both univariate and multivariate analyses showed Raf-1 (P = 0.000, P = 0.010), p-Raf-1 (P = 0.004, P = 0.046), or both (P = 0.001, P = 0.016) was good prognostic markers for poor survival rate in NSCLC patients. Suppression of Raf-1 inhibited tumorigenesis by inducing apoptosis both in vitro and in vivo. These findings demonstrate that overexpression of Raf-1, p-Raf-1 or both could be considered as a new independent prognostic biomarker for poor survival rates for NSCLC patients.