title: Clinicopathological and Prognostic Value of Ki-67 Expression in Bladder Cancer: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Ki-67 is an established marker of cell proliferation, and the Ki-67 index correlates with the clinical course of several cancer types, including bladder cancer (BC). However, the clinicopathological and prognostic significance of Ki-67 in bladder cancer remains unclear. Therefore, we performed a systematic review and meta-analysis to clarify this relationship.
  
  
  METHODS
  A comprehensive literature search for relevant studies published up to February 1, 2016, was performed using PubMed, Cochrane Library, Embase and ISI Web of Knowledge. The effects of Ki-67 expression on survival outcome in patients with BC and BC subtypes were evaluated. Furthermore, the relationship between Ki-67 expression and the clinicopathological features of BC were assessed.
  
  
  RESULTS
  Thirty-one studies with 5147 bladder cancer patients were selected for evaluation. Ki-67 expression was significantly associated with shorter recurrence-free (HR 1.69, 95% CI: 1.33-2.14), progression-free (HR 1.89, 95% CI: 1.43-2.51), overall (HR 2.03, 95% CI: 1.31-3.16), and cancer-specific (HR 1.69, 95% CI: 1.47-1.95) survival. Moreover, whereas high expression was more common in high tumor stage, recurrence status, tumor size, there was no correlation between high Ki-67 expression and age, gender, smoking habits, and tumor number. Importantly, analysis of the different subgroups of BC suggested that significant correlations between high Ki-67 expression and survival outcome (recurrence-free/progression-free/overall/cancer-specific survival) are present only in European-American patients.
  
  
  CONCLUSIONS
  The present results indicate that over-expression of Ki-67 is distinctly correlated with poor patient survival. Ki-67 may serve as a valuable biomarker for prognosis in BC patients, particularly in non-Asian BC patients. The results suggest no significant association between Ki-67 expression and BC prognosis in Asian patients. Further efforts are needed to fully clarify this relationship.
authors.affiliation: Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Gansu Province for Urological Diseases, Clinical Center of Gansu Province for Nephro-urology, Lanzhou University, Lanzhou, China.
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Gansu Province for Urological Diseases, Clinical Center of Gansu Province for Nephro-urology, Lanzhou University, Lanzhou, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Gansu Province for Urological Diseases, Clinical Center of Gansu Province for Nephro-urology, Lanzhou University, Lanzhou, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Gansu Province for Urological Diseases, Clinical Center of Gansu Province for Nephro-urology, Lanzhou University, Lanzhou, China.
authors.forename: Mingguo
authors.initials: M
authors.lastname: Li
authors.affiliation: Department Gastroenterology, The Second Hospital of Lanzhou University, Lanzhou University, Lanzhou, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Gansu Province for Urological Diseases, Clinical Center of Gansu Province for Nephro-urology, Lanzhou University, Lanzhou, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
authors.affiliation: Department of Urology, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, United States of America.
authors.forename: Hanzhang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Urology, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Svatek
authors.affiliation: Department of Urology, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, United States of America.
authors.forename: Ronald
authors.initials: R
authors.lastname: Rodriguez
authors.affiliation: Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Gansu Province for Urological Diseases, Clinical Center of Gansu Province for Nephro-urology, Lanzhou University, Lanzhou, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Wang
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D019394:Ki-67 Antigen