title: CDK1 and CDK2 activity is a strong predictor of renal cell carcinoma recurrence.
abstract: BACKGROUND
  In renal cell carcinoma (RCC), the prediction of metastasis via tumor prognostic markers remains a major problem. The objective of our study was to evaluate the efficacy of cyclin-dependent kinase (CDK)1 and CDK2 activity as a prognostic marker in human RCC.
  
  
  METHODS
  Surgical specimens were obtained from 125 patients with RCC without metastasis. Protein expression and kinase activity of CDKs were analyzed using a newly developed assay system named C2P (Sysmex, Kobe, Japan). We then examined the specific activities (SAs) of CDK1 and CDK2 and calculated CDK2SA-CDK1SA ratio in RCC. Also, risk score (RS) was examined.
  
  
  RESULTS
  A total of 125 cases were tested, though 34 cases were excluded because of low sample quality (25 cases) and assay failure (9 cases). In total, 91 cases were analyzed. They included 68 male and 23 female patients, ranging in age from 19 to 83 years. At a median follow-up of 36 months (1-109M), tumor with low CDK2SA-CDK1SA ratio showed significantly better 5-year recurrence-free survival than those with high CDK2SA-CDK1SA ratio (88.7% vs. 54.7%, P = 0.00141). Also, RS enabled the classification of RCCs into high-risk and low-risk groups, and patients with tumors classified as low RS showed better recurrence-free survival than patients with tumors with high RS (88.7% vs. 54.7%, P = 0.0141).
  
  
  CONCLUSIONS
  CDK1SA of tumors and the CDK2SA are both associated with recurrence and prognosis.
  
  
  CONCLUSIONS
  CDK-based risk demonstrated is strongly associated with clinical outcome. CDK-based risk should be an accurate system for predicting recurrence and survival for planning follow-up.
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: fhongo@koto.kpu-m.ac.jp.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Hongo
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Takaha
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Oishi
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Terukazu
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Naitoh
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Naya
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kamoi
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Okihara
authors.affiliation: Central Research Laboratories, Sysmex Corporation, Kobe, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Matsushima
authors.affiliation: Central Research Laboratories, Sysmex Corporation, Kobe, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakayama
authors.affiliation: Central Research Laboratories, Sysmex Corporation, Kobe, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishihara
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016203:CDC2 Protein Kinase; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000473:pathology; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases
keywords: Biomarker; Cyclin-dependent kinase; Renal cell carcinoma