Landen Charles N, Lin Yvonne G, Immaneni Anand, Deavers Michael T, Merritt William M, Spannuth Whitney A, Bodurka Diane C, Gershenson David M, Brinkley William R, Sood Anil K
Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Clin Cancer Res. 2007 Jul 15;13(14):4098-104. doi: 10.1158/1078-0432.CCR-07-0431.
To assess the clinical significance of Aurora-A kinase, a centrosome-regulating serine-threonine kinase, in ovarian carcinoma.
Aurora-A kinase expression was assessed by Western blot (cell lines) or immunohistochemistry (high-grade epithelial ovarian cancers), and clinical variables were collected by retrospective chart review. Centrosome amplification was assessed by immunofluorescence in cell lines, and by immunohistochemistry in patient samples.
All ovarian cancer cell lines exhibited significant Aurora-A kinase protein overexpression, and all except A2780-par had centrosome amplification, a characteristic of mitotic dysregulation leading to genomic instability. Fifty-eight of 70 patient samples (82.8%) exhibited Aurora-A kinase overexpression compared with normal ovarian surface epithelium. High Aurora-A kinase expression was strongly associated with supernumerary centrosome count in tumor cells (P<0.001). Tumors with the greatest Aurora-A overexpression (n=24) had decreased patient survival (median survival, 1.44 versus 2.81 years; P=0.01). High Aurora-A expression and suboptimal surgical cytoreduction remained predictors of poor survival (P<0.05) by multivariate analysis.
Aurora-A kinase is overexpressed by a substantial proportion of ovarian cancers and is associated with centrosome amplification and poor survival. It may be a useful prognostic marker and target in ovarian cancer.
评估中心体调节丝氨酸 - 苏氨酸激酶Aurora - A激酶在卵巢癌中的临床意义。
通过蛋白质印迹法（细胞系）或免疫组织化学法（高级别上皮性卵巢癌）评估Aurora - A激酶表达，并通过回顾性病历审查收集临床变量。通过细胞系中的免疫荧光和患者样本中的免疫组织化学评估中心体扩增。
所有卵巢癌细胞系均表现出Aurora - A激酶蛋白的显著过表达，除A2780 - par外所有细胞系均有中心体扩增，这是导致基因组不稳定的有丝分裂失调的特征。与正常卵巢表面上皮相比，70例患者样本中有58例（82.8%）表现出Aurora - A激酶过表达。Aurora - A激酶高表达与肿瘤细胞中多余中心体数量密切相关（P<0.001）。Aurora - A过表达程度最高的肿瘤（n = 24）患者生存率降低（中位生存期，1.44年对2.81年；P = 0.01）。多因素分析显示，Aurora - A高表达和手术细胞减灭不充分仍然是生存率低的预测因素（P<0.05）。
相当一部分卵巢癌中Aurora - A激酶过表达，且与中心体扩增和低生存率相关。它可能是卵巢癌中一个有用的预后标志物和治疗靶点。
