• Open Access

Aurora-A activation, correlated with hypoxia-inducible factor-1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma

Authors

  • Xiang-Bo Wan,

    1. Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
    2. Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
    3. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
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    • These authors contributed equally to this work.
  • Xin-Juan Fan,

    1. Department of Pathology, Gastrointestinal Institute, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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    • These authors contributed equally to this work.
  • Pei-Yu Huang,

    1. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
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    • These authors contributed equally to this work.
  • Dong Dong,

    1. Department of Otorhinolaryngology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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  • Yan Zhang,

    1. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
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  • Ming-Yuan Chen,

    1. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
    2. Department of Nasopharyngeal Carcinoma, Cancer Center of Sun Yat-sen University, Guangzhou, China
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  • Jin Xiang,

    1. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
    2. Department of Pathology, Cancer Center of Sun Yat-sen University, Guangzhou, China
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  • Jie Xu,

    1. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
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  • Li Liu,

    1. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
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  • Wei-Hua Zhou,

    1. Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
    2. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
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  • Yan-Chun Lv,

    1. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
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  • Xiang-Yuan Wu,

    1. Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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  • Ming-Huang Hong,

    Corresponding author
    1. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
    2. Department of Nasopharyngeal Carcinoma, Cancer Center of Sun Yat-sen University, Guangzhou, China
    3. Clinical Trials Center, Cancer Center of Sun Yat-sen University, Guangzhou, China
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  • Quentin Liu

    Corresponding author
    1. Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
    2. Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
    3. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China
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Abstract

Previously, we and others showed that hypoxia-inducible factor-1α (HIF-1α) and transcriptionally upregulated Aurora-A were required for disease progression in several tumors. Here, we address the clinicopathologic value of Aurora-A and HIF-1α in locally advanced nasopharyngeal carcinoma (NPC). Aurora-A and HIF-1α expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a randomized controlled trial. Of these patients, 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy, and acted as the training set, and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were used as the testing set to validate the prognostic effect of Aurora-A and HIF-1α. We found that Aurora-A and HIF-1α were highly expressed in NPC, but were deficient in normal adjacent epithelia. In the testing set, Aurora-A overexpression predicted a shortened 5-year overall survival (59.1% vs 82.5%, P = 0.024), progression-free survival (44.8% vs 79.8%, P = 0.004), and distant metastasis-free survival (43.0% vs 17.3%, P = 0.016). Multivariate regression analysis confirmed that Aurora-A was indeed an independent prognostic factor for death, recurrence, and distant metastasis both in the testing set and overall patients. Moreover, a positive correlation between Aurora-A and HIF-1α was detected (P = 0.037). Importantly, although HIF-1α did not show any prognostic effect for patient outcome, the subset with Aurora-A and HIF-1α co-overexpression had the poorest overall, progression-free, and distant metastasis-free survival (all P < 0.05). Our results confirmed that Aurora-A was an independent prognostic factor for NPC. Aurora-A combined with HIF-1α refined the risk definition of the patient subset, thus potentially directing locally advanced NPC patients for more selective therapy. (Cancer Sci, doi: 10.1111/j.1349-7006.2012.02332.x, 2012)

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