Aurora-A contributes to cisplatin resistance and lymphatic metastasis in non-small cell lung cancer and predicts poor prognosis.
Aurora-A contributes to cisplatin resistance and lymphatic metastasis in non-small cell lung cancer and predicts poor prognosis.
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Aurora-A 导致非小细胞肺癌顺铂耐药和淋巴转移并预测不良预后
DOI：
10.1186/1479-5876-12-200
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发表时间：
2014-07-31
影响因子：
7.4
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Xu J;Yue CF;Zhou WH;Qian YM;Zhang Y;Wang SW;Liu AW;Liu Q
研究背景含铂化疗可提高非小细胞肺癌（NSCLC）患者的生存率，但由于耐药，疗效有限。在这项研究中，我们的目的是确定Aurora-A蛋白的表达及其与顺铂耐药和预后NSCLC。MethodsWe采用免疫组化分析，以确定Aurora-A蛋白的表达在102例NSCLC患者手术和辅助顺铂为基础的化疗。采用Kaplan-Meier生存估计和考克斯模型评估预后意义。通过表达载体和小分子干扰RNA转染及小分子抑制剂转染，研究Aurora-A在非小细胞肺癌顺铂耐药调控中的潜在作用多因素分析显示，胃癌的预后与淋巴结转移（p = 0.018）、淋巴结转移（p = 0.038）和复发（p= 0.005）有关。Aurora-A的高表达预示着较低的总生存期（OS）和无进展生存期（PFS）;体外研究表明，Aurora-A在顺铂耐药的肺癌细胞中表达升高，过表达或敲低Aurora-A可导致细胞对顺铂的耐药性增加或降低。此外，Aurora-A的抑制逆转了cisplatin-resistant cells.ConclusionsThe目前的研究结果表明，Aurora-A的高表达与顺铂为基础的化疗耐药性，并预测在NSCLC患者的生存差的迁移能力。Aurora-A可能作为药物反应的预测生物标志物和逆转化疗耐药的治疗靶点。
BackgroundPlatinum-based chemotherapy improves survival among patients with non-small cell lung cancer (NSCLC), but the efficiency is limited due to resistance. In this study, we aimed to identify the expression of Aurora-A and its correlation with cisplatin resistance and prognosis in NSCLC.MethodsWe used immunohistochemical analysis to determine the expression of Aurora-A protein in 102 NSCLC patients treated by surgery and adjuvant cisplatin-based chemotherapy. The prognostic significances were assessed by Kaplan-Meier survival estimates and Cox models. The potential role of Aurora-A in the regulation of cisplatin resistance in NSCLC cells was examined by transfections using expression vector and small interfering RNA or using small-molecule inhibitors.ResultsAurora-A expression was significantly associated with clinical stage (p= 0.018), lymph node metastasis (p= 0.038) and recurrence (p= 0.005), and was an independent prognostic parameter in multivariate analysis. High level of Aurora-A expression predicted poorer overall survival (OS) and progression-free survival (PFS).In vitrodata showed that Aurora-A expression was elevated in cisplatin-resistant lung cancer cells, and overexpression or knockdown of Aurora-A resulted in increased or decreased cellular resistance to cisplatin. Furthermore, inhibition of Aurora-A reversed the migration ability of cisplatin-resistant cells.ConclusionsThe current findings suggest that high Aurora-A expression is correlated with cisplatin-based chemotherapeutic resistance and predicts poor patient survival in NSCLC. Aurora-A might serve as a predictive biomarker of drug response and therapeutic target to reverse chemotherapy resistance.
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DOI：
10.1016/j.bbagrm.2010.09.004
发表时间：
2010-10
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Katayama H;Sen S
通讯作者：
Sen S
DOI：
10.1056/nejmoa1214271
发表时间：
2013-03-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Friboulet L;Olaussen KA;Pignon JP;Shepherd FA;Tsao MS;Graziano S;Kratzke R;Douillard JY;Seymour L;Pirker R;Filipits M;André F;Solary E;Ponsonnailles F;Robin A;Stoclin A;Dorvault N;Commo F;Adam J;Vanhecke E;Saulnier P;Thomale J;Le Chevalier T;Dunant A;Rousseau V;Le Teuff G;Brambilla E;Soria JC
通讯作者：
Soria JC
影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
45.3
作者：
Friedberg, Jonathan W.;Mahadevan, Daruka;Bernstein, Steven H.
通讯作者：
Bernstein, Steven H.
影响因子：
11.5
作者：
Cheng, Ai-Lan;Huang, Wei-Guo;Xiao, Zhi-Qiang
通讯作者：
Xiao, Zhi-Qiang