Is APC hypermethylation a diagnostic biomarker for bladder cancer? A meta-analysis

Objective: Numerous studies have been performed to investigate the association between APC promoter hypermethylation and bladder cancer risk. Nevertheless, the conclusion was uncertain due to small sample size, different ethnicities, and tumor subtype. Hence, to accurately assess the effect of APC promoter hypermethylation on the risk of bladder cancer, we performed the meta-analysis. Materials and methods: We retrieved the relevant literatures from electronic databases such as PubMed, Web of Science, Wanfang, Vapp, and CNKI (Chinese National Knowledge Infrastructure). 95% CI and OR were calculated to evaluate the associations of APC promoter hypermethylation with risk and clinical features of bladder cancer. Heterogeneity among studies was assessed with Q test and P statistic. In addition, the diagnostic sensitivity, specificity, and area under the curve (AUC) value of APC hypermethylation for bladder cancer were calculated. Results: In total, 14 articles with 531 controls and 1,293 cases were included to assess the associations of APC promoter hypermethylation with the risk and clinical characteristics of bladder cancer. The significant association between APC promoter hypermethylation and bladder cancer risk was detected (OR =17.01, CI =7.40-39.07). Furthermore, the results revealed that APC promoter hypermethylation was significantly correlated with the grade of bladder tumor (pTNM stage: OR =1.84, CI =0.87.-3.93; grade: OR =4.11, CI =1.62-10.43). According to the results of diagnostic evaluation, the diagnostic sensitivity, specificity, and AUC value of APC hypermethylation for bladder cancer risk were 0.52 (95% CI =0.41-0.63), 0.98 (95% CI =0.90-1.00), and 0.80 (95% CI =0.76-0.83), respectively. Conclusion: This meta-analysis revealed that APC promoter hypermethylation was a risk factor for bladder cancer risk. In addition, APC promoter hypermethylation was significantly associated with the grade of bladder cancer. APC hypermethylation might be a useful biomarker for the clinical diagnosis of bladder cancer.