Abstract
BackgroundPlatinum-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.MethodsWe 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.ResultsAurora-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.ConclusionsThe 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.
Highlights
Platinum-based chemotherapy improves survival among patients with non-small cell lung cancer (NSCLC), but the efficiency is limited due to resistance
Aurora-A expression and kinase activity are increased during late G2 to M phase, and its subcellular localization dynamically changes during the cell cycle [10]
Aurora-A expression in NSCLC tissues The specificity for antibody targeting Aurora-A was showed in Additional file 1: Figure S1 by western blot analysis
Summary
Platinum-based chemotherapy improves survival among patients with non-small cell lung cancer (NSCLC), but the efficiency is limited due to resistance. Much work remains to be done to validate the clinical relevance of resistance genes to benefit from adjuvant platinum-based chemotherapy. Aurora-A ( called STK15/BTAK) is a member of serine/threonine kinase family. It is involved in various mitotic events, such as centrosome maturation and separation, mitotic entry, bipolar-spindle assembly, chromosome alignment on the metaphase plate and cytokinesis. Aurora-A serves as a promising target in cancer therapy, and several small-molecule inhibitors for Aurora-A kinase are currently being investigated within clinical trials [19]. The novel Aurora-A kinase inhibitor alisertib (MLN8237) is currently undergoing evaluation in a phase I/II trial with paclitaxel in recurrent ovarian cancer [20]. The inhibitor alisertib seems clinically active in both B- and T-cell aggressive lymphomas, and confirmatory single-agent and combination studies have been initiated [21]
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