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. 2017 May 9;8(19):31509-31520.
doi: 10.18632/oncotarget.15663.

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

Yuhua Ma  1   2 , Jie Yang  1 , Ruozheng Wang  2 , Zegao Zhang  1 , Xiaoli Qi  1 , Chunhua Liu  1 , Miaomiao Ma  1
Affiliations

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

Yuhua Ma et al. Oncotarget. .

Abstract

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.

Keywords: Aurora kinase A; Uyghur; cell cycle; cervical squamous cell carcinoma; radiation.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declared no potential conflict of interest with respect to the authorship and/or publication of this article.

Figures

Figure 1
Figure 1. Expression of AURKA in CSCC
The intensity of the dye color was graded as 0 (no color), 1 (light yellow), 2 (light brown) or 3 (brown), and the number of positive cells was graded as 0 (no staining), 1 (<30%), 2 (30%-60%) and 3 (>60%); the two grades were added together and the specimens were assigned to one of four levels as follows: a score of 0-1 (-), a score of 2 (+), a score of 3-4 (++), a score of more than 5 (+++). Immunostaining was considered to be low (-, +) or high (++, +++).
Figure 2
Figure 2. Recurrence-free survival (RFS) and overall survival (OS) curves, and the association between AURKA expression and survival
RFS curve (A) and OS curve (B), respectively, and the 5-year RFS and OS were 23.26% and 27.91%, respectively. (C-D) Kaplan-Meier plots of (C) RFS and (D) OS in 129 patients with CSCC according to AURKA expression. The P values for survival comparison, which were obtained by log-rank test, were all less than 0.05.
See this image and copyright information in PMC

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