Open AccessA urora‐ A activation, correlated with hypoxia‐inducible factor‐1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma
Author(s) -
Wan XiangBo,
Fan XinJuan,
Huang PeiYu,
Dong Dong,
Zhang Yan,
Chen MingYuan,
Xiang Jin,
Xu Jie,
Liu Li,
Zhou WeiHua,
Lv YanChun,
Wu XiangYuan,
Hong MingHuang,
Liu Quentin
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02332.x
Subject(s) - nasopharyngeal carcinoma , medicine , radiation therapy , immunohistochemistry , metastasis , chemoradiotherapy , chemotherapy , downregulation and upregulation , hypoxia (environmental) , oncology , tumor progression , tumor hypoxia , carcinoma , pathology , cancer , biology , biochemistry , chemistry , organic chemistry , oxygen , gene
Previously, we and others showed that hypoxia‐inducible factor‐1α ( HIF ‐1α) and transcriptionally upregulated A urora‐ A were required for disease progression in several tumors. Here, we address the clinicopathologic value of A urora‐ A and HIF ‐1α in locally advanced nasopharyngeal carcinoma ( NPC ). A urora‐ 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 A urora‐ A and HIF ‐1α. We found that A urora‐ A and HIF ‐1α were highly expressed in NPC , but were deficient in normal adjacent epithelia. In the testing set, A urora‐ 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 A urora‐ 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 A urora‐ 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 A urora‐ 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 A urora‐ A was an independent prognostic factor for NPC . A urora‐ 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)