RESEARCH ARTICLE
DAPK Promoter Methylation and Bladder Cancer Risk: A Systematic Review and MetaAnalysis Lihe Dai☯, Chong Ma☯, Zhensheng Zhang, Shuxiong Zeng, Anwei Liu, Shijie Tang, Qian Ren, Yinghao Sun, Chuanliang Xu* Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China ☯ These authors contributed equally to this work. *
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Abstract a11111
Background
OPEN ACCESS Citation: Dai L, Ma C, Zhang Z, Zeng S, Liu A, Tang S, et al. (2016) DAPK Promoter Methylation and Bladder Cancer Risk: A Systematic Review and Meta-Analysis. PLoS ONE 11(12): e0167228. doi:10.1371/journal.pone.0167228 Editor: Shengtao Zhou, West China Second Hospital, Sichuan University, CHINA
Methylation of tumor suppressor gene promoter leads to transcription inactivation and is involved in tumorigenesis. Several studies demonstrate a potential association between the Death-Associated Protein Kinase (DAPK) gene promoter methylation and bladder cancer risk, tumor stage and histological grade. Due to inconsistent results of these studies, we performed this meta-analysis to ascertain the association.
Methods Studies were retrieved from the PubMed, Embase, Web of Science and the Cochrane Library databases. Study selection and data extraction were executed by two reviewers independently. Meta-analysis was performed using Stata 13.0 and Review Manager 5.3 software.
Received: June 10, 2016 Accepted: November 10, 2016 Published: December 1, 2016 Copyright: © 2016 Dai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The authors received no specific funding for this work. Competing Interests: The authors have declared that no competing interests exist.
Results A total of 21 articles involving 15 case control and 8 case series studies were included in this meta-analysis. DAPK promoter methylation was associated with bladder cancer risk (OR: 5.81; 95%CI = 3.83–8.82, P0.05 and I2 values < 50%, the fixed-effects model (the Mantel-Haenszel method) were selected. Otherwise, a random-effects model (the DerSimonian and Laird method) was applied. In addition, a sensitivity analysis was performed to assess the stability of the results. The potential publication bias was examined in a funnel plot visually and the degree of asymmetry was tested by Egger’s test[27]. This meta-analysis was performed using the software STATA version 13.0 (Stata Corporation, TX, USA) and Review Manager 5.3(Cochrane Collaboration, Oxford, UK). All P-values were based on twosided tests and a P
