title: Cell cycle progression score predicts metastatic progression of clear cell renal cell carcinoma after resection.
abstract: BACKGROUND
  The outcome of surgically resected, apparently localized, clear cell renal carcinoma (ccRCC) is uncertain.
  
  
  OBJECTIVE
  To evaluate if cell cycle progression (CCP) gene expression can predict future metastasis.
  
  
  METHODS
  Pathologic T2a-T3b tumors at University of Iowa were reviewed. Patients with known or suspected metastasis, lymph node involvement or who received neoadjuvant or adjuvant radiation, chemotherapy or immunotherapy were excluded. Case and control cohorts were defined as those who did or did not develop metastatic disease within 5 years. Measured levels of 31 cell cycle genes and 15 control genes from the tumor were calculated as a CCP score. Additionally, gene expression data for a separate ccRCC cohort was downloaded from The Cancer Genome Atlas (TCGA).
  
  
  RESULTS
  Univariate analysis of 26 cases and 38 controls revealed that the CCP score predicted progression to metastasis (OR 2.65, p = 0.0091). In multivariate logistic regression modeling, CCP expression remained a significant independent predictor for progression (p = 0.026). The CCP score was also significantly associated with distant metastasis in the TCGA renal cancer cohort in both univariate (p = 1.0 × 10-9) and multivariate (p = 5.6 × 10-3) analysis.
  
  
  CONCLUSIONS
  The CCP score has prognostic value in predicting metastatic progression after resection of organ-confined ccRCC.
authors.affiliation: Department of Urology, University of Iowa, IA, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Askeland
authors.affiliation: Department of Urology, University of Iowa, IA, USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Chehval
authors.affiliation: Department of Pathology, University of Iowa, IA, USA.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Askeland
authors.affiliation: Myriad Genetics, University of Iowa, IA, USA.
authors.forename: Placede G
authors.initials: PG
authors.lastname: Fosso
authors.affiliation: Myriad Genetics, University of Iowa, IA, USA.
authors.forename: Zaina
authors.initials: Z
authors.lastname: Sangale
authors.affiliation: Myriad Genetics, University of Iowa, IA, USA.
authors.forename: Nafei
authors.initials: N
authors.lastname: Xu
authors.affiliation: Myriad Genetics, University of Iowa, IA, USA.
authors.forename: Saradha
authors.initials: S
authors.lastname: Rajamani
authors.affiliation: Myriad Genetics, University of Iowa, IA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Stone
authors.affiliation: Department of Urology, University of Iowa, IA, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Brown
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000556:secondary* / Q000601:surgery; D016022:Case-Control Studies; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins
keywords: Clear cell renal cell carcinoma; biological markers; kidney cancer; metastasis