title: p21-activated kinase 1 predicts recurrence and survival in patients with non-metastatic clear cell renal cell carcinoma.
abstract: OBJECTIVE
  To estimate the impact of p21-activated kinase 1 expression on recurrence and survival of patients with non-metastatic clear cell renal cell carcinoma after surgical resection.
  
  
  METHODS
  We retrospectively enrolled 254 patients (187 in the training cohort and 67 in the validation cohort) with non-metastatic clear cell renal cell carcinoma undergoing nephrectomy at a single institution. Clinicopathological features, overall survival and recurrence-free survival were recorded. p21-activated kinase 1 intensities were assessed by immunohistochemistry of patients' specimens. The Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on overall survival and recurrence-free survival. The concordance index was calculated to assess predictive accuracy.
  
  
  RESULTS
  In both cohorts, elevated p21-activated kinase 1 expression in tumor tissues positively correlated with advanced T stage and Fuhrman grade. High p21-activated kinase 1 expression indicated poor survival and early recurrence of patients with non-metastatic clear cell renal cell carcinoma, especially with early T1-2 stage disease. After backward elimination, p21-activated kinase 1 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of the traditional University of California Integrated Staging System and Mayo Clinic stage, size, grade and necrosis prognostic models was improved when p21-activated kinase 1 expression was added.
  
  
  CONCLUSIONS
  Elevated expression of p21-activated kinase 1 seems to be an independent adverse prognostic biomarker for recurrence and survival in patients with non-metastatic clear cell renal cell carcinoma after nephrectomy.
authors.affiliation: Department of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.forename: Le
authors.initials: L
authors.lastname: Xu
authors.forename: Huimin
authors.initials: H
authors.lastname: An
authors.forename: Weisi
authors.initials: W
authors.lastname: Liu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009392:Nephrectomy; D011379:Prognosis; D012189:Retrospective Studies; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C515903:PAK1 protein, human; D054462:p21-Activated Kinases
keywords: clear cell renal cell carcinoma; overall survival; p21-activated kinase 1; prognostic biomarker; recurrence-free survival