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Aurora-A contributes to cisplatin resistance and lymphatic metastasis in non-small cell lung cancer and predicts poor prognosis.

AbstractBACKGROUND:
Platinum-based chemotherapy improves survival among patients with non-small cell lung cancer (NSCLC), but the efficiency is limited due to resistance. In this study, we aimed to identify the expression of Aurora-A and its correlation with cisplatin resistance and prognosis in NSCLC.
METHODS:
We used immunohistochemical analysis to determine the expression of Aurora-A protein in 102 NSCLC patients treated by surgery and adjuvant cisplatin-based chemotherapy. The prognostic significances were assessed by Kaplan-Meier survival estimates and Cox models. The potential role of Aurora-A in the regulation of cisplatin resistance in NSCLC cells was examined by transfections using expression vector and small interfering RNA or using small-molecule inhibitors.
RESULTS:
Aurora-A expression was significantly associated with clinical stage (p = 0.018), lymph node metastasis (p = 0.038) and recurrence (p = 0.005), and was an independent prognostic parameter in multivariate analysis. High level of Aurora-A expression predicted poorer overall survival (OS) and progression-free survival (PFS). In vitro data showed that Aurora-A expression was elevated in cisplatin-resistant lung cancer cells, and overexpression or knockdown of Aurora-A resulted in increased or decreased cellular resistance to cisplatin. Furthermore, inhibition of Aurora-A reversed the migration ability of cisplatin-resistant cells.
CONCLUSIONS:
The current findings suggest that high Aurora-A expression is correlated with cisplatin-based chemotherapeutic resistance and predicts poor patient survival in NSCLC. Aurora-A might serve as a predictive biomarker of drug response and therapeutic target to reverse chemotherapy resistance.
AuthorsJie Xu, Cai-feng Yue, Wei-hua Zhou, Yuan-min Qian, Yan Zhang, Shao-wu Wang, An-wen Liu, Quentin Liu
JournalJournal of translational medicine (J Transl Med) Vol. 12 Pg. 200 ( 2014) ISSN: 1479-5876 [Electronic] England
PMID25082261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • Aurora Kinase A
  • Cisplatin
Topics
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Aurora Kinase A (genetics, physiology)
  • Biomarkers, Tumor (metabolism)
  • Carcinoma, Non-Small-Cell Lung (diagnosis, drug therapy, pathology)
  • Cisplatin (therapeutic use)
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Lung Neoplasms (diagnosis, drug therapy, pathology)
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prognosis
  • Tumor Cells, Cultured

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