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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
- Source :
- British Journal of Cancer
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Background: 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). Methods: 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. Results: 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 (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). Conclusions: 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.
- Subjects :
- Adult
Oncology
Cancer Research
medicine.medical_specialty
endocrine system diseases
medicine.medical_treatment
Internal medicine
Biomarkers, Tumor
medicine
Carcinoma
Humans
Molecular Diagnostics
neoplasms
Survival analysis
Aged
Chemotherapy
Predictive marker
biology
Cyclin-dependent kinase 4
business.industry
Endometrial cancer
low risk
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 6
Middle Aged
Prognosis
medicine.disease
Survival Analysis
Endometrial Neoplasms
cyclin-dependent kinase
Ki-67 Antigen
Chemotherapy, Adjuvant
endometrial cancer
biology.protein
Biomarker (medicine)
Female
chemo-sensitivity
Neoplasm Recurrence, Local
Ki-67 expression
business
Carcinoma, Endometrioid
Adjuvant
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 113
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....60f6a43f284b33ef6c9e848b297b5c87
- Full Text :
- https://doi.org/10.1038/bjc.2015.369