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有丝分裂激酶Aurora-A对原发性十二指肠腺癌的预后价值

Prognosis value of mitotic kinase Aurora-A for primary duodenal adenocarcinoma.

作者信息

Chen Jie, Lin Qu, Wen Jing-Yun, Li Xing, Ma Xiao-Kun, Fan Xin-Juan, Cao Qin-Hua, Dong Min, Wei Li, Chen Zhan-Hong, Li Xiao-Yun, Wang Tian-Tian, Liu Quentin, Wan Xiang-Bo, Xing Yan-Fang, Wu Xiang-Yuan

机构信息

Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.

出版信息

Tumour Biol. 2014 Sep;35(9):9361-70. doi: 10.1007/s13277-014-2215-3. Epub 2014 Jun 20.

Abstract

Others and we have demonstrated that hypoxia-inducible factor 1α (HIF-1α) and transcriptionally upregulated Aurora-A are required for disease progression in several tumors. We investigated the clinicopathological value of HIF-1α and Aurora-A in primary duodenal adenocarcinoma (PDA). Using immunohistochemistry, we evaluated Aurora-A and HIF-1α expression semiquantitatively in 140 PDA cases. There were 76 cases from one institute that formed the training set; 64 cases from another two institutes were used as the testing set to validate the prognostic value of Aurora-A and HIF-1α expression. Aurora-A expression was high or sufficient in the tumor zone, whereas expression was low in the adjacent normal epithelia. High Aurora-A expression, identified using the training set receiver operator characteristic (ROC) analysis-generated cutoff score, predicted poorer overall survival both in the testing set (18.0 vs. 45.1 %, P = 0.001) and training set (23.1 vs. 53.9 %, P = 0.011). Multivariate Cox regression confirmed that Aurora-A was an independent prognostic factor. Contrary to previous studies, we did not detect any correlation between Aurora-A and HIF-1α. Survival analysis showed that HIF-1α level was not correlated with patient outcome (P = 0.466). Activation of Aurora-A, an independent negative prognostic biomarker, might be used to identify particular PDA patients for more selective therapy.

摘要

我们和其他研究人员已经证明,缺氧诱导因子1α(HIF-1α)以及转录上调的极光激酶A(Aurora-A)是几种肿瘤疾病进展所必需的。我们研究了HIF-1α和Aurora-A在原发性十二指肠腺癌(PDA)中的临床病理价值。我们采用免疫组织化学方法,对140例PDA病例中的Aurora-A和HIF-1α表达进行了半定量评估。其中76例来自一个机构,构成训练集;另外两个机构的64例用作测试集,以验证Aurora-A和HIF-1α表达的预后价值。Aurora-A在肿瘤区域的表达较高或充足,而在相邻正常上皮中的表达较低。使用训练集的受试者工作特征(ROC)分析生成的临界值确定的高Aurora-A表达,在测试集(18.0%对45.1%,P = 0.001)和训练集(23.1%对53.9%,P = 0.011)中均预测总体生存率较差。多变量Cox回归证实Aurora-A是一个独立的预后因素。与先前的研究相反,我们未检测到Aurora-A与HIF-1α之间存在任何相关性。生存分析表明,HIF-1α水平与患者预后无关(P = 0.466)。极光激酶A作为一个独立的负性预后生物标志物,其激活可用于识别特定的PDA患者,以便进行更具选择性的治疗。

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