Ma Yuhua, Yang Jie, Wang Ruozheng, Zhang Zegao, Qi Xiaoli, Liu Chunhua, Ma Miaomiao
Radiotherapy Second Department, People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang, China.
The Department of Radiation Oncology, Tumor Hospital Affilated To Xinjiang Medical University, Urumqi, Xinjiang, China.
Oncotarget. 2017 May 9;8(19):31509-31520. doi: 10.18632/oncotarget.15663.
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.
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.
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.
Aurora-A may serve as a predictive biomarker of radiation response and a therapeutic target to reverse radiation therapy resistance.
根治性放射治疗（RT）（联合或不联合基于顺铂的化疗）是宫颈鳞状细胞癌（CSCC）最有效的治疗方法之一，但由于耐药性，其疗效有限。在本研究中，我们调查了Aurora激酶A（Aurora-A，AURKA）的表达与CSCC患者放疗反应之间的关系。
采用免疫组织化学方法检测129例维吾尔族CSCC患者未经治疗的原发性肿瘤活检标本中Aurora-A的表达。这些患者的主要治疗方法是根治性根治性放疗，包括盆腔放疗加近距离放疗（A点总剂量：70-85 Gy）（联合或不联合基于顺铂的化疗）。评估肿瘤Aurora-A表达的预后价值和患者的临床结局。
Aurora-A表达与淋巴结转移（P<0.001）、肿瘤体积大（P<0.001）、血红蛋白（Hb）水平低（P=0.011）和复发（P<0.001）显著相关，但与其他临床病理因素无关。Aurora-A高表达患者的根治性放疗效果不佳（P<0.001）。在129例入组患者中，单因素分析显示，淋巴结转移、肿瘤体积大、Hb水平低和AURKA过表达是无复发生存期（RFS）和总生存期（OS）的预后因素。然而，在多因素分析中，只有高AURKA表达是RFS（风险比，3.953；95%CI，1.473-10.638；P=0.006）和OS（风险比9.091；95%CI 2.597-32.258；P<0.001）的不良独立危险因素。
Aurora-A可作为放疗反应的预测生物标志物和逆转放疗耐药性的治疗靶点。
