J Cancer 2017; 8(8):1484-1491. doi:10.7150/jca.18553

Research Paper

Overexpression of PAK1 Correlates with Aberrant Expression of EMT Markers and Poor Prognosis in Non-Small Cell Lung Cancer

Zhiying Yang1*, Heran Wang2*, Longzheng Xia2, Linda Oyang2, Yujuan Zhou2, Baihua Zhang2, Xiaoyan Chen2, Xia Luo2, Qianjin Liao2✉, Jianping Liang2✉

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.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Yang Z, Wang H, Xia L, Oyang L, Zhou Y, Zhang B, Chen X, Luo X, Liao Q, Liang J. Overexpression of PAK1 Correlates with Aberrant Expression of EMT Markers and Poor Prognosis in Non-Small Cell Lung Cancer. J Cancer 2017; 8(8):1484-1491. doi:10.7150/jca.18553. Available from https://www.jcancer.org/v08p1484.htm

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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.