Raf1 is a prognostic factor for progression in patients with non‑small cell lung cancer after radiotherapy.

Raf-1 proto-oncogene, serine/threonine kinase (Raf1) acts as a part of the RAS/RAF/MEK/ERK signaling pathway and regulates cell migration, apoptosis and differentiation. However, few studies are available on the expression and clinical significance of Raf1 in non-small cell lung cancer (NSCLC). This study investigated the clinical value and prognostic significance of Raf1 in NSCLC patients, following radiotherapy. We evaluated the Raf1 expression using immunohistochemical analyses of samples from 110 NSCLC patients who received radiotherapy. The association between Raf1 expression and clinicopathological variables was also analyzed. The multivariate Cox proportional hazard model was used to determine the prognostic value of Raf1 in regards to progression and 3-year survival. Significant associations between Raf1 expression and invasion and metastasis capability in lung cancer A549 and H1299 cell lines were identified. Results showed that 44.5% (49/110) of the NSCLC patient specimens demonstrated Raf1 expression, which was found to be positively correlated with lymph node metastasis (P=0.014), T stage (P=0.038) and poor histological differentiation (P=0.029). Later progression was observed in patients with negative or low Raf1 expression than in patients with high Raf1 expression (P=0.002). The multivariate analysis indicated that Raf1 is an independent prognostic factor for time to progression (TTP) (HR, 1.94; 95% CI, 1.16-3.25; P=0.01). A high Raf1 expression was found to result in a poor 3-year overall survival (OS)(HR, 1.64; 95% CI, 0.98-2.75; P=0.06). Raf1 overexpression was correlated with early progression in NSCLC. Raf1 may serve as a novel prognostic factor and potential target for improving the long-term outcome of NSCLC patients.