Clinicopathological and Prognostic Value of Ki-67 Expression in Bladder Cancer: A Systematic Review and Meta-Analysis

• Published in: PloS one Vol. 11; no. 7; p. e0158891
• Main Authors: Tian, Yuejun, Ma, Zhiming, Chen, Zhaohui, Li, Mingguo, Wu, Zhiping, Hong, Mei, Wang, Hanzhang, Svatek, Robert, Rodriguez, Ronald, Wang, Zhiping
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.07.2016; Public Library of Science (PLoS)
• Subjects: Analysis; Bioindicators; Biology and Life Sciences; Biomarkers; Bladder; Bladder cancer; Cancer; Care and treatment; Cell cycle; Cell proliferation; Clinical pathology; Correlation; Gene Expression Regulation, Neoplastic; Humans; Ki-67 antigen; Ki-67 Antigen - genetics; Ki-67 Antigen - metabolism; Laboratories; Medical ethics; Medical prognosis; Medicine and Health Sciences; Meta-analysis; Multivariate analysis; Overexpression; Patients; Physical Sciences; Prognosis; Research and Analysis Methods; Smoking; Squamous cell carcinoma; Statistical analysis; Studies; Subgroups; Survival; Systematic review; Tumors; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Urology; United States > US; Texas; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158891

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. 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. 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. 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.