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Prognostic significance of TOP2A expression in bladder cancer: Systematic review and meta-analysis
Ahmad Zulfan Hendri1, Robert Robert1, Toni Febriyanto1
1Division of Urology, Department of Surgery, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada/ Dr. Sardjito General Hospital, Yogyakarta, Indonesia.
Introduction:
Elevated topoisomerase IIA (TOP2A) expression is consistently linked to poor prognosis, driving cancer progression through its role in DNA unlinking. Although TOP2A is well-established in other cancers, its prognostic value in bladder cancer remains unclear. This study was conducted to assess the prognostic significance of TOP2A for patients with bladder cancer.
Methods:
PubMed, EMBASE (Ovid), and the Cochrane Library were systematically searched to identify studies published up to August 8, 2024. Published studies reporting the prognosis of patients with bladder cancer stratified by TOP2A expression were included. A random-effect model was used to pool the standardized mean difference (SMD) with 95% confidence interval (CI) for tumor stage and grade and hazard ratio (HR) with 95% CI for cancer-specific survival (CSS). The Newcastle-Ottawa Quality (NOS) was used to assess the risk of bias in the included studies.
Results:
Nine studies with 1764 eligible patients with bladder cancer were identified. TOP2A expression was found in 32% patients with bladder cancer. High TOP2A expression was significantly correlated with higher tumor grade (SMD 1.61, 95% CI -0.02-3.23, p=0.05), higher tumor stage (SMD 1.09, 95% CI 0.01-2.17, p=0.05), and worse CSS (HR 1.19, 95% CI 1.05-1.36, p=0.008) in patients with bladder cancer.
Conclusions:
TOP2A expression shows potential as a prognostic biomarker in bladder cancer; however, significant heterogeneity in study design, measurement methods, and analytical approaches limits the strength of the current evidence. Further prospective studies with standardized biomarker assessment are warranted to validate its clinical utility.
