title: The Prognostic Role of Ki-67/MIB-1 in Upper Urinary-Tract Urothelial Carcinomas: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Upper urinary-tract urothelial carcinomas (UTUC) constitute 5% of urothelial malignancies. Prognostic biomarkers would allow lower risk surgical approaches for less aggressive UTUCs. One biomarker-Ki-67/mindbomb E3 ubiquitin protein ligase 1 (Ki-67/MIB-1)-shows promise in UTUC, but there have been conflicting findings regarding its prognostic role. The systematic review and meta-analysis aim to determine the prognostic value of Ki-67/MIB-1 in UTUC in terms of UTUC-specific mortality rate, 5-year disease-free survival, and 5-year overall survival (including disease-specific survival).
  
  
  METHODS
  A systematic review of the current literature produced 654 records. A total of 13 studies consisting of 1030 patients were finally included in the meta-analysis. Hazard ratios (HRs) with 95% confidence intervals (CI) were extracted or estimated. The individual HR estimates were combined into a pooled HR using a fixed-effects model that summed homogeneity of the individual true HRs.
  
  
  RESULTS
  Patients with Ki-67/MIB-1 overexpression displayed significantly higher UTUC-specific mortality rate (pooled HR: 2.14, 95% CI: 1.73-2.64; p<0.00001), significantly reduced 5-year disease-free survival (pooled HR: 2.27, 95% CI: 1.79-2.92; p<0.00001), and significantly reduced 5-year overall survival (pooled HR=1.77; 95% CI: 1.39-2.23 p<0.00001). There was significant heterogeneity detected in the UTUC-specific mortality rate meta-analysis (I(2)=63%) and the 5-year disease-free survival meta-analysis (I(2)=65%), but there was no significant heterogeneity detected in the 5-year overall survival meta-analysis (I(2)=0%). Egger's testing showed that none of the outcomes were influenced by publication bias (p>0.05).
  
  
  CONCLUSIONS
  Ki-67/MIB-1 overexpression shows promise as a prognostic biomarker for UTUC patients and requires further investigation.
authors.affiliation: 1 Department of Urology, Xiangya Hospital, Central South University , Changsha, China .
authors.forename: Ye
authors.initials: Y
authors.lastname: Lei
authors.affiliation: 2 Department of General Surgery, Xiangya Hospital, Central South University , Changsha, China .
authors.forename: Zengbo
authors.initials: Z
authors.lastname: Li
authors.affiliation: 1 Department of Urology, Xiangya Hospital, Central South University , Changsha, China .
authors.forename: Lin
authors.initials: L
authors.lastname: Qi
authors.affiliation: 1 Department of Urology, Xiangya Hospital, Central South University , Changsha, China .
authors.forename: Shiyu
authors.initials: S
authors.lastname: Tong
authors.affiliation: 3 Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University , Shijiazhuang, China .
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: 1 Department of Urology, Xiangya Hospital, Central South University , Changsha, China .
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: 1 Department of Urology, Xiangya Hospital, Central South University , Changsha, China .
authors.forename: Minfeng
authors.initials: M
authors.lastname: Chen
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007682:Kidney Pelvis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D014516:Ureteral Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D019394:Ki-67 Antigen