Aurora-A affects radiosenstivity in cervical squamous cell carcinoma and predicts poor prognosis.
Aurora-A affects radiosenstivity in cervical squamous cell carcinoma and predicts poor prognosis.
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DOI：
10.18632/oncotarget.15663
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发表时间：
2017-05-09
期刊：
影响因子：
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通讯作者：
Ma M
中科院分区：
文献类型：
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作者：
Ma Y;Yang J;Wang R;Zhang Z;Qi X;Liu C;Ma M
确定性放射治疗(RT)是治疗宫颈鳞癌(CSCC)最有效的方法之一，但由于耐药，疗效有限。在本研究中，我们探讨了宫颈鳞癌患者中Aurora-A(Aurora-A，AURKA)的表达与放疗反应的关系。应用免疫组织化学方法检测129例维吾尔族宫颈鳞癌患者未经治疗的原发灶活检标本中Aurora-A的表达。这些患者的主要治疗是明确的根治性放疗，包括盆腔放疗加近距离放射治疗(A点总剂量：70~85GY)(加或不加以顺铂为基础的化疗)。评估肿瘤Aurora-A表达的预后价值和患者的临床预后。Aurora-A的表达与淋巴结转移(P<；0.001)、肿瘤大小(P<；0.001)、低血红蛋白(P=0.011)和复发(P<；0.001)显著相关，而与其他临床病理因素无关。明确的RT对于Aurora-A高表达的患者是不利的(P <； 0.001)。单因素分析显示，在129例入选患者中，淋巴结转移、肿瘤大小、低Hb水平和AURKA过度表达是影响复发无瘤生存期(RFS)和总生存期(OS)的预后因素。然而，在多因素分析中，只有AURKA的高表达是RFS(危险比3.953；95%CI，1.473-10.638；P=0.006)和OS(危险比9.091；95%CI 2.597-32.258；P<；0.001)的不利独立危险因素。Aurora-A可作为辐射反应的预测生物标志物和逆转放射治疗耐药的治疗靶点。
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.