Rac1 overexpression is correlated with epithelial mesenchymal transition and predicts poor prognosis in non-small cell lung cancer.

Objective: Ras-related C3 botulinum toxin substrate1(Rac1) and epithelial mesenchymal transition (EMT) are key therapeutic targets in cancer. We investigated the clinical significance of Rac1 and markers of EMT expression in non-small cell lung cancer (NSCLC), and their possible correlation with EMT phenotype. Methods: Immunohistochemistry was used to assess the expression of Rac1, Snail1, Twist1, N-cadherin (N-cad), Vimentin (Vim), and E-cadherin (E-cad) in 153 NSCLC paraffin-embedded specimens and 45 normal specimens adjacent to tumors. The correlation of Rac1 and EMT markers with clinicopathological characteristics and the relationship between the protein levels and progression-free survival (PFS) and overall survival (OS) were analyzed. Results: Compared with non-tumor tissues, the NSCLC tissues showed marked elevation in the levels of Rac1, Snail1, Twist1, N-cad, and Vim levels, whereas the E-cad levels were significantly decreased (P < 0.05). The aberrant expression of Rac1 and EMT markers was significantly associated with TNM stage and metastasis (P < 0.05). Increased expression of Rac1 may be associated with poor OS and PFS compared with low expression (P<0.001 and P=0.004). Significant correlations were observed between the EMT markers expressed and OS or PFS(P<0.01). In addition, multivariate analysis indicated that the expression of Rac1, Snail1, Twist1, N-cad, Vim, and E-cad was an independent prognostic factor in NSCLC. Interestingly, Rac1 expression was positively correlated with Snail1, Twist1, N-cad, and Vim levels (r=0.563, r=0.440, r=0.247 r=0.536, P<0.01, respectively) and negatively correlated with E-cad levels (r=-0.464, P<0.001) in NSCLC tissues. Rac1, Twist, Snail1, Vim and N-cad were highly expressed in lung cancer patients resistant to radiotherapy, while E-cad was poorly expressed. Conclusion: Rac1 may promote NSCLC progression and metastasis via EMT, which may be considered as a potential therapeutic target.