Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer.

Abstract

BACKGROUND AND OBJECTIVE:

Aurora A, as a member of serine/threonine kinase family and a common characteristic of epithelial cancers, plays a critical role in cell mitosis. However, the clinical significance of Aurora A in non-small cell lung cancer (NSCLC) remains undetermined.

METHODS:

The expression of Aurora A in NSCLC and paired normal adjacent lung tissues was determined by immunohistochemistry, Western blot, and reverse transcriptase polymerase chain reaction. Receiver operating characteristic (ROC) curve analysis was employed to determine a cutoff score for Aurora A expression in a training set (n=135). For validation, the ROC-derived cutoff score was subjected to analysis of the association of Aurora A expression with patient outcome and clinicopathological characteristics in a testing set (n=128) and overall patients (n=263). The correlation of Aurora A with cisplatin resistance and epithelial-mesenchymal transition (EMT) was examined in vitro in NSCLC cells by overexpression or knockdown of Aurora A.

RESULTS:

Aurora A expression was significantly upregulated in tumor tissues compared with paired normal tissues (P<.01). The expression of Aurora A was closely associated with clinical stage, lymph node metastasis, and recurrence and was an independent prognostic parameter in multivariate analysis. High level of Aurora A expression predicted poorer overall survival and disease-free survival in NSCLC patients treated with cisplatin-based adjuvant chemotherapy. In vitro data showed that overexpression or knockdown of Aurora A resulted in increased or decreased cellular resistance to cisplatin. Furthermore, inhibition of Aurora A reversed the EMT process.

CONCLUSIONS:

Aurora A was identified as an inferior prognostic and cisplatin-resistant biomarker in NSCLC patients, which provided potential evidences for therapeutic target and reversing drug resistance.

• Authors: Peng Kuang, Zuhua Chen, JiaYuan Wang, Zhentao Liu, Jingyuan Wang, Jing Gao, Lin Shen
• Journal: Translational oncology (Transl Oncol) Vol. 10 Issue 3 Pg. 367-377 (Jun 2017) ISSN: 1936-5233 [Print] United States
• PMID: 28431392 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.