Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non–Small Cell Lung Cancer
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 expressi...
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doaj-69952ce1db5b4c88af5e24d55bccd2b32020-11-25T00:39:52ZengElsevierTranslational Oncology1936-52332017-06-01103367377Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non–Small Cell Lung CancerPeng Kuang0Zuhua Chen1JiaYuan Wang2Zhentao Liu3Jingyuan Wang4Jing Gao5Lin Shen6Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and InstituteDepartment of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and InstituteDepartment of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and InstituteDepartment of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and InstituteDepartment of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and InstituteDepartment of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and InstituteAddress all correspondence to: Lin Shen, Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China.; Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and InstituteBACKGROUND 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.http://www.sciencedirect.com/science/article/pii/S1936523317300712 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Peng Kuang Zuhua Chen JiaYuan Wang Zhentao Liu Jingyuan Wang Jing Gao Lin Shen |
spellingShingle |
Peng Kuang Zuhua Chen JiaYuan Wang Zhentao Liu Jingyuan Wang Jing Gao Lin Shen Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non–Small Cell Lung Cancer Translational Oncology |
author_facet |
Peng Kuang Zuhua Chen JiaYuan Wang Zhentao Liu Jingyuan Wang Jing Gao Lin Shen |
author_sort |
Peng Kuang |
title |
Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non–Small Cell Lung Cancer |
title_short |
Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non–Small Cell Lung Cancer |
title_full |
Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non–Small Cell Lung Cancer |
title_fullStr |
Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non–Small Cell Lung Cancer |
title_full_unstemmed |
Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based Chemotherapy in Patients with Non–Small Cell Lung Cancer |
title_sort |
characterization of aurora a and its impact on the effect of cisplatin-based chemotherapy in patients with non–small cell lung cancer |
publisher |
Elsevier |
series |
Translational Oncology |
issn |
1936-5233 |
publishDate |
2017-06-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S1936523317300712 |
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