1. Department of Histology and Embryology, Medical College, Hunan normal University, Changsha 410013, PR China;
2. 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: p21-activated kinases (PAKs) are serine/threonine protein kinases. PAK1 and epithelial-mesenchymal transition (EMT) are key therapeutic targets in cancer. The clinical significance of PAK1 and its potential association with EMT phenotype in non-small cell lung cancer (NSCLC) was investigated.
Methods: Immunohistochemistry was used to detect the expression of PAK1, and mesenchymal and epithelial markers (vimentin, N-cadherin, and E-cadherin) in 186 cases of NSCLC tissues and 50 cases of tumor-adjacent normal tissues. The correlation of PAK1 with the clinicopathological characteristics, prognosis, and mesenchymal and epithelial markers in NSCLC were analyzed.
Results: Compared with the non-tumor tissues, PAK1, vimentin, and N-cadherin levels were markedly elevated in NSCLC tissues, whereas the E-cadherin levels were significantly decreased (P<0.05). The aberrant expression of PAK1 was significantly associated with TNM stage and metastasis (P<0.001). Patients who displayed high expression of PAK1 may achieve a poorer progression-free survival (PFS) and overall survival (OS), compared to those with low expression of PAK1 (P=0.001 and P<0.001). Univariate and multivariate analysis showed that high expression of PAK1 was an independent predictor of poor prognosis [hazard ratio (HR) =2.121, P<0.001, HR=1.928, P=0.001, respectively]. In addition, significant correlations were observed between the EMT markers and OS or PFS (P<0.01). Interestingly, PAK1 expression was positively correlated with vimentin and N-cadherin levels (r=0.473, P<0.001; r=0.526, P<0.001, respectively) and negatively correlated with E-cadherin levels (r=-0.463, P<0.001) in NSCLC tissues.
Conclusion: PAK1 may promote NSCLC progression and metastasis through EMT, thereby exhibiting the potential of an efficient prognostic predictor in NSCLC patients.
Keywords: PAK1, non-small cell lung cancer, epithelial-mesenchymal transition, prognosis, metastasis.