Predictive value of Aurora-A/STK15 expression for late stage epithelial ovarian cancer patients treated by adjuvant chemotherapy
Predictive value of Aurora-A/STK15 expression for late stage epithelial ovarian cancer patients treated by adjuvant chemotherapy
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DOI：
10.1158/1078-0432.ccr-06-2775
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发表时间：
2007-07-15
影响因子：
11.5
通讯作者：
Werner, Martin
中科院分区：
文献类型：
--
作者：
Lassmann, Silke;Shen, Yi;Werner, Martin
目的：研究中心体激酶Aurora-A/STK 15（AURKA）在上皮性卵巢癌中的表达和调节，并确定该标志物对接受不同辅助化疗的晚期上皮性卵巢癌患者的预后和预测价值。通过显微切割和定量逆转录酶-聚合酶链反应（RT-PCR）分析卵巢上皮癌（n = 115）和非肿瘤性卵巢（n = 28）的存档切除标本中AURKA mRNA和蛋白的表达。PCR和免疫组化。用荧光原位杂交法检测37例患者的AURKA DNA拷贝数。结果：AURKA mRNA表达在肿瘤中显著升高（P < 0.001），且与AURKA蛋白表达相关（P = 0.0134）。107例中有68例（63.5%）检测到AURKA蛋白的过表达，并与AURKA DNA拷贝数增加（P = 0.0141）和着丝粒20异倍体（P = 0.0137）相关。此外，AURKA过表达与接受紫杉醇/卡铂治疗的最佳减容患者的总生存率改善相关（n = 43，P = 0.018）。最后，在一个探索性的方法，患者接受非紫杉烷为基础的治疗，AURKA过表达是预测较差的总生存率（n = 30，P = 0.049）。结论：AURKA过表达被认为是在大多数晚期上皮性卵巢癌，最有可能是由于增加AURKA DNA拷贝数和/或染色体20异倍体。重要的是，AURKA过表达可能会不同程度地影响紫杉烷和非紫杉烷为基础的辅助治疗反应。该研究揭示了AURKA在体内上皮癌中的表达和调控，并特别显示了其作为临床相关标志物和潜在治疗靶点的价值。
Purpose: To investigate the expression and regulation of the centrosomal kinase Aurora-A/STK15 (AURKA) in epithelial ovarian cancers and to determine the prognostic and predictive value of this marker for patients with late stage epithelial ovarian cancer treated by distinct adjuvant chemotherapies.Experimental Design: Archival resection specimens of epithelial ovarian cancers (n = 115) and nonneoplastic ovaries (n = 28) were analyzed for AURKA mRNA and protein expression by microdissection and quantitative reverse transcriptase-PCR and immunohistochemistry. AURKA DNA copy numbers were measured by fluorescence in situ hybridization in 37 cases. Statistical evaluation was done with respect to clinicopathologic variables, disease-free survival, and overall survival.Results: AURKA mRNA expression was significantly elevated in cancers (P < 0.001) and correlated with AURKA protein expression (P = 0.0134). Overexpression of AURKA protein was detected in 68 of 107 (63.5%) cases and was linked with increased AURKA DNA copy numbers (P = 0.0141) and centromere 20 aneusomy (P = 0.0137). Moreover, AURKA overexpression was associated with improved overall survival in optimal debulked patients receiving taxol/carboplatin therapy (n = 43, P = 0.018). Finally, in an exploratory approach, patients receiving non-taxane-based therapy, AURKA overexpression was predictive for worse overall survival (n = 30, P = 0.049).Conclusions: AURKA overexpression is seen in the majority of late stage epithelial ovarian cancers, most likely due to increased AURKA DNA copy numbers and/or chromosome 20 aneusomy. Importantly, AURKA overexpression may differentially affect taxane and non-taxane-based adjuvant therapy responses. The study sheds new light on AURKA expression and regulation in epithelial cancers in vivo and specifically shows its value as a clinically relevant marker and as a potential therapeutic target per se.