Abstract
BackgroundKi-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.MethodsA 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.ResultsThirty-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.ConclusionThe 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.
Highlights
Bladder cancer (BC) is a common cancer of the urinary tract, with an estimated 429,800 new cases of bladder cancer (BC) and 165,100 deaths annually worldwide [1]
Ki-67 expression was significantly associated with shorter recurrence-free (HR 1.69, 95% confidence intervals (CIs): 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
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
Summary
Bladder cancer (BC) is a common cancer of the urinary tract, with an estimated 429,800 new cases of BC and 165,100 deaths annually worldwide [1]. Ki-67 is a predictive factor for tumor development, and its expression has been correlated with poor prognosis in several types of cancer [7,8,9,10]. Chen et al [11] confirmed that Ki-67 was an independent predictor of tumor recurrence and progression in a study of 72 cases of NMIBC. Makboul and Gontero et al [12, 13] demonstrated that Ki-67 was only an independent predictor of progression and not recurrence in NMIBC patients. Studies have revealed that Ki-67 is not correlated with or an independent predictor of BC recurrence, progression, and death. The clinicopathological and prognostic significance of Ki-67 in bladder cancer remains unclear. We performed a systematic review and meta-analysis to clarify this relationship
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