title: Aurora-A activation, correlated with hypoxia-inducible factor-1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma.
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.
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiang-Bo
authors.initials: XB
authors.lastname: Wan
authors.forename: Xin-Juan
authors.initials: XJ
authors.lastname: Fan
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Huang
authors.forename: Dong
authors.initials: D
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Xiang
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Zhou
authors.forename: Yan-Chun
authors.initials: YC
authors.lastname: Lv
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Wu
authors.forename: Ming-Huang
authors.initials: MH
authors.lastname: Hong
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
mesh_terms: D064127:Aurora Kinases; D015153:Blotting, Western; D059248:Chemoradiotherapy; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000628:therapy; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011836:Radiation Tolerance; D016019:Survival Analysis; D014158:Transcription, Genetic / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases