Abstract

BackgroundDefinitive 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.MethodsThe 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.ResultsAurora-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.ConclusionsAurora-A may serve as a predictive biomarker of radiation response and a therapeutic target to reverse radiation therapy resistance.

Highlights

  • Cervical cancer (CC) is the fourth most common malignant tumor in women worldwide, with 528,000 new cases in 2012 [1]

  • Aurora-A may serve as a predictive biomarker of radiation response and a therapeutic target to reverse radiation therapy resistance

  • We investigated the relationship between the expression of Aurora-A and the response to radiation therapy (RT) or Concurrent chemoradiation therapy (CCRT) in patients with cervical squamous cell carcinoma (CSCC)

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Summary

Introduction

Cervical cancer (CC) is the fourth most common malignant tumor in women worldwide, with 528,000 new cases in 2012 [1]. 87% of CC cases occur in developing countries. The morbidity rate due to CC in China is among the highest in the world [2]. Uyghur women who live in the southern region of Xinjiang Province, China, have the highest morbidity (590/100,000) [3] due to CC in the country. Squamous cell carcinoma (SCC) accounts for approximately 95% of all CCs [4]. CC tends to develop in Uyghur women at a younger age. 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. We investigated the relationship between the expression of Aurora kinase A (Aurora-A, AURKA)and response to RT in patients with CSCC

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