4.3 Article

Aurora-A affects radiosenstivity in cervical squamous cell carcinoma and predicts poor prognosis

Journal

ONCOTARGET
Volume 8, Issue 19, Pages 31509-31520

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15663

Keywords

Aurora kinase A; cervical squamous cell carcinoma; radiation; Uyghur; cell cycle

Funding

  1. Natural Science Foundation of China Xinjiang Uygur Autonomous Region [2015211C211]
  2. International Cooperation Projects of Ministry of Science and Technology [2012DFA31560]

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Background: Definitive radiation therapy (RT) (with or without cisplatin-based chemotherapy) is one of the most effective treatments for cervical squamous cell carcinoma (CSCC), but efficacy is limited due to resistance. In the present study, we investigated the relationship between the expression of Aurora kinase A (Aurora-A, AURKA) and response to RT in patients with CSCC. Methods: The expression of Aurora-A in biopsy specimens of untreated primary tumors in 129 Uyghur patients with CSCC was investigated immunohistochemically. Primary treatment in these patients was definitive radical RT, which consisted of pelvic RT plus brachytherapy (total point A dose: 70-85 Gy) (with or without cisplatin-based chemotherapy). The prognostic value of tumoral Aurora-A expression and patients' clinical outcomes were evaluated. Results: Aurora-A expression was significantly associated with lymph node metastasis (P<0.001), large tumor size (P<0.001), low hemoglobin (Hb) level (P=0.011) and recurrence (P<0.001), but not other clinicopathological factors. Definitive RT was unfavorable in patients with high Aurora-A expression (P < 0.001). In 129 enrolled patients, lymph node metastasis, large tumor size, low Hb level, and AURKA overexpression were prognostic factors for both recurrent free survival (RFS) and overall survival (OS) in univariate analysis. However, only high AURKA expression was an adverse independent risk factor for both RFS (hazard ratio, 3.953; 95% CI, 1.473-10.638; P = 0.006) and OS (hazard ratio 9.091; 95% CI 2.597-32.258; P<0.001) in multivariate analyses. Conclusions: Aurora-A may serve as a predictive biomarker of radiation response and a therapeutic target to reverse radiation therapy resistance.

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