Key Laboratory of Translational Radiation Oncology, Hunan Province, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China.
*These authors contributed equally to this work.
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.
Keywords: non-small cell lung cancer, Rac1, epithelial-mesenchymal transition, prognosis, markers, radiotherapy.