Department of Obstetrics and Gynecology, Diakonischen Dienste Hannover GmbH, Diakoniekrankenhaus Henriettenstiftung und Diakoniekrankenhaus Friederikenstift, Hanover, Germany.
BMC Cancer. 2012 Nov 27;12:562. doi: 10.1186/1471-2407-12-562.
Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA) are currently being developed. Here, we examine the prognostic impact of AURKA in node-negative breast cancer patients without adjuvant systemic therapy (n = 766).
AURKA was analyzed using microarray-based gene-expression data from three independent cohorts of node-negative breast cancer patients. In multivariate Cox analyses, the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER), and HER2 were considered.
Patients with higher AURKA expression had a shorter metastasis-free survival (MFS) in the Mainz (HR 1.93; 95% CI 1.34 - 2.78; P < 0.001), Rotterdam (HR 1.95; 95% CI 1.45- 2.63; P<0.001) and Transbig (HR 1.52; 95% CI 1.14-2.04; P=0.005) cohorts. AURKA was also associated with MFS in the molecular subtype ER+/HER2- carcinomas (HR 2.10; 95% CI 1.70-2.59; P<0.001), but not in ER-/HER2- nor in HER2+ carcinomas. In the multivariate Cox regression adjusted to age, grade and tumor size, AURKA showed independent prognostic significance in the ER+/HER2- subtype (HR 1.73; 95% CI 1.24-2.42; P=0.001). Prognosis of patients in the highest quartile of AURKA expression was particularly poor. In addition, AURKA correlated with the proliferation metagene (R=0.880; P<0.001), showed a positive association with grade (P<0.001), tumor size (P<0.001) and HER2 (P<0.001), and was inversely associated with ER status (P<0.001).
AURKA is associated with worse prognosis in estrogen receptor positive breast carcinomas. Patients with the highest AURKA expression (>75% percentile) have a particularly bad prognosis and may profit from therapy with AURKA inhibitors.
目前正在开发针对细胞周期调控的极光激酶 A（AURKA）的抑制剂。在这里，我们研究了无辅助系统治疗的淋巴结阴性乳腺癌患者（n = 766）中 AURKA 的预后影响。
使用来自三个独立的淋巴结阴性乳腺癌患者队列的基于微阵列的基因表达数据分析 AURKA。在多变量 Cox 分析中，考虑了年龄、组织学分级、肿瘤大小、雌激素受体（ER）和 HER2 的预后影响。
在美因茨（HR 1.93；95%CI 1.34-2.78；P < 0.001）、鹿特丹（HR 1.95；95%CI 1.45-2.63；P<0.001）和 Transbig（HR 1.52；95%CI 1.14-2.04；P = 0.005）队列中，AURKA 表达较高的患者转移无复发生存率（MFS）较短。AURKA 还与 ER+/HER2- 癌的 MFS 相关（HR 2.10；95%CI 1.70-2.59；P<0.001），但与 ER-/HER2- 或 HER2+ 癌无关。在调整年龄、分级和肿瘤大小的多变量 Cox 回归中，AURKA 在 ER+/HER2- 亚组中具有独立的预后意义（HR 1.73；95%CI 1.24-2.42；P = 0.001）。AURKA 表达最高四分位数的患者预后尤其差。此外，AURKA 与增殖代谢基因（R = 0.880；P<0.001）相关，与分级呈正相关（P<0.001），与肿瘤大小（P<0.001）和 HER2（P<0.001）呈正相关，与 ER 状态呈负相关（P<0.001）。
AURKA 与雌激素受体阳性乳腺癌的预后不良相关。AURKA 表达最高（>75%分位数）的患者预后特别差，可能受益于 AURKA 抑制剂治疗。
