Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy.
Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy.
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DOI：
10.1038/bjc.2015.369
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发表时间：
2015-11-17
影响因子：
8.8
通讯作者：
Fujii T
中科院分区：
文献类型：
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作者：
Ikeda Y;Oda K;Ishihara H;Wada-Hiraike O;Miyasaka A;Kashiyama T;Inaba K;Fukuda T;Sone K;Matsumoto Y;Arimoto T;Maeda D;Ikemura M;Fukayama M;Kawana K;Yano T;Aoki D;Osuga Y;Fujii T
病理低危的子宫内膜癌患者不接受术后治疗；但10-15%的患者出现复发，预后较差。我们评估了细胞周期蛋白依赖性激酶4/6 （CDK4/6）活性的临床重要性，以及它作为子宫内膜样子宫内膜癌（EEC）预后和化疗敏感性的新生物标志物的意义。用细胞周期分析（C2P）方法检测了109例EEC患者肿瘤样本中周期蛋白依赖性激酶4/6的表达和酶活性。测定cdk4 /6特异性活性（CDK4/6SA），并分析其与临床病理因素及Ki-67表达的关系。cdk4 /6特异性活性与Ki-67有显著相关性（P=0.035），与其他临床病理特征无显著相关性。病理低危患者（未接受辅助化疗，n=74）的CDK4/6SA明显高于中危或高危患者（接受辅助化疗，n=35） （P=0.002）。此外，高CDK4/6SA（>3.0）患者的无进展生存期（PFS）显著（P=0.024）短于低CDK4/6SA（<3.0）患者。虽然Ki-67表达本身不是预后的标志，但高CDK4/6SA和高Ki-67表达（>15%）的联合与较短的PFS密切相关（P=0.015），并且这种联合是低危险组的独立预后不良因素。相反，在中/高危组中，CDK4/6SA高的患者比CDK4/6SA低的患者有更好的预后趋势（P=0.063）。cdk4 /6特异性活性可作为预测预后和可能的化疗敏感性的生物标志物。Ki-67联合表达可能会增强CDK4/6SA作为生物标志物的临床应用价值。
Pathologically low-risk endometrial cancer patients do not receive postoperative treatment; however, 10–15% of these patients show recurrence with poor prognosis. We evaluated the clinical importance of cyclin-dependent kinase 4/6 (CDK4/6) activity, and its significance as a novel biomarker for the prognosis and chemo-sensitivity of endometrioid endometrial carcinoma (EEC). Cyclin-dependent kinase 4/6 expression and enzyme activity in 109 tumour samples from patients with EEC were examined with a cell-cycle profiling (C2P) assay. CDK4/6-specific activity (CDK4/6SA) was determined, and its relationship with clinicopathological factors and expression of Ki-67 was analysed. CDK4/6-specific activity was significantly correlated with Ki-67 (P=0.035), but not with any other clinicopathological characteristics. CDK4/6SA was significantly higher (P=0.002) in pathologically low-risk patients (not receiving adjuvant chemotherapy, n=74) than in intermediate- or high-risk patients (receiving adjuvant chemotherapy, n=35). In addition, patients with high CDK4/6SA (>3.0) showed significantly (P=0.024) shorter progression-free survival (PFS) than those with low CDK4/6SA (<3.0). Although Ki-67 expression itself was not a marker for prognosis, the combination of high CDK4/6SA and high Ki-67 expression (>15%) was robustly associated with shorter PFS (P=0.015), and this combination was an independent poor prognostic factor in the low-risk group. Inversely, in the intermediate-/high-risk group, patients with high CDK4/6SA had a tendency of a more favourable prognosis compared with patients with low CDK4/6SA (P=0.063). CDK4/6-specific activity can be used as a biomarker to predict prognosis and, possibly, chemo-sensitivity. The combination of Ki-67 expression might strengthen the clinical usefulness of CDK4/6SA as a biomarker.