Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy

Yuji Ikeda, Katsutoshi Oda, Hideki Ishihara, Osamu Wada-Hiraike, Aki Miyasaka, Tomoko Kashiyama, Kanako Inaba, Tomohiko Fukuda, Kenbun Sone, Yoko Matsumoto, Takahide Arimoto, Daichi Maeda, Masako Ikemura, Masahi Fukayama, Kei Kawana, Tetsu Yano, Daisuke Aoki, Yutaka Osuga, Tomoyuki Fujii

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1477-1483
Number of pages7
JournalBritish Journal of Cancer
Volume113
Issue number10
DOIs
Publication statusPublished - 2015 Nov 17

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Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase 4
Adjuvant Chemotherapy
Endometrial Neoplasms
Recurrence
Endometrioid Carcinoma
Biomarkers
Disease-Free Survival
Cell Cycle

Keywords

  • chemo-sensitivity
  • cyclin-dependent kinase
  • endometrial cancer
  • Ki-67 expression
  • low risk

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy. / Ikeda, Yuji; Oda, Katsutoshi; Ishihara, Hideki; Wada-Hiraike, Osamu; Miyasaka, Aki; Kashiyama, Tomoko; Inaba, Kanako; Fukuda, Tomohiko; Sone, Kenbun; Matsumoto, Yoko; Arimoto, Takahide; Maeda, Daichi; Ikemura, Masako; Fukayama, Masahi; Kawana, Kei; Yano, Tetsu; Aoki, Daisuke; Osuga, Yutaka; Fujii, Tomoyuki.

In: British Journal of Cancer, Vol. 113, No. 10, 17.11.2015, p. 1477-1483.

Research output: Contribution to journalArticle

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 2015, 'Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy', British Journal of Cancer, vol. 113, no. 10, pp. 1477-1483. https://doi.org/10.1038/bjc.2015.369
Ikeda, Yuji ; Oda, Katsutoshi ; Ishihara, Hideki ; Wada-Hiraike, Osamu ; Miyasaka, Aki ; Kashiyama, Tomoko ; Inaba, Kanako ; Fukuda, Tomohiko ; Sone, Kenbun ; Matsumoto, Yoko ; Arimoto, Takahide ; Maeda, Daichi ; Ikemura, Masako ; Fukayama, Masahi ; Kawana, Kei ; Yano, Tetsu ; Aoki, Daisuke ; Osuga, Yutaka ; Fujii, Tomoyuki. / Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy. In: British Journal of Cancer. 2015 ; Vol. 113, No. 10. pp. 1477-1483.
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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.",
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T1 - Prognostic importance of CDK4/6-specific activity as a predictive marker for recurrence in patients with endometrial cancer, with or without adjuvant chemotherapy

AU - Ikeda, Yuji

AU - Oda, Katsutoshi

AU - Ishihara, Hideki

AU - Wada-Hiraike, Osamu

AU - Miyasaka, Aki

AU - Kashiyama, Tomoko

AU - Inaba, Kanako

AU - Fukuda, Tomohiko

AU - Sone, Kenbun

AU - Matsumoto, Yoko

AU - Arimoto, Takahide

AU - Maeda, Daichi

AU - Ikemura, Masako

AU - Fukayama, Masahi

AU - Kawana, Kei

AU - Yano, Tetsu

AU - Aoki, Daisuke

AU - Osuga, Yutaka

AU - Fujii, Tomoyuki

PY - 2015/11/17

Y1 - 2015/11/17

N2 - 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.

AB - 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.

KW - chemo-sensitivity

KW - cyclin-dependent kinase

KW - endometrial cancer

KW - Ki-67 expression

KW - low risk

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