Association between DAPK1 promoter methylation and cervical cancer: a meta-analysis.

Jiaqiang Xiong,Lilan Yang,Jinjin Zhang,Kecheng Huang,Lanfang Ma,Zhiyong Lu,Aiyue Luo,Meixia Lu,Shuhong Yang,Shixuan Wang,Hao Shi,Ya Li,Xuefeng Liu

doi:10.1371/journal.pone.0107272

Jiaqiang Xiong, Lilan Yang + Show 11 more

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https://doi.org/10.1371/journal.pone.0107272

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Abstract

BackgroundDeath-associated protein kinase1 (DAPK1) is an important tumor suppressor gene. DNA methylation can inactivate genes, which has often been observed in the carcinogenesis of cervical cancer. During the past several decades, many studies have explored the association between DAPK1 promoter methylation and cervical cancer. However, many studies were limited by the small samples size and the findings were inconsistent among them. Thus, we conducted a meta-analysis to assess the association between DAPK1 promoter methylation and cervical cancer.MethodsWe systematically searched eligible studies in the PubMed, Web of Science, EMBASE and CNKI databases. Using meta-regression, subgroup analysis and sensitivity analysis, we explored the potential sources of heterogeneity. The odds ratio (OR) and 95% confidence interval (95% CI) were calculated by Meta-Analysis in R.ResultsA total of 15 studies from 2001 to 2012, comprising 818 tumor tissues samples and 671 normal tissues samples, were analyzed in this meta-analysis. The frequencies of DAPK1 promoter methylation ranged from 30.0% to 78.6% (median, 59.3%) in cervical cancer tissue and 0.0% to 46.7% (median, 7.8%) in normal cervical tissue. The pooled OR was 19.66 (95%CI = 8.72–44.31) with the random effects model, and heterogeneity was found through the sensitivity analysis. The I2 = 60% (P = 0.002) decreased to I2 = 29.2% (P = 0.144) when one heterogeneous study was excluded, and the pooled OR increased to 21.80 (95%CI = 13.44–35.36) with the fixed effects model.ConclusionThe results suggested a strong association between DAPK1 promoter methylation and cervical cancer. This study also indicated that DAPK1 promoter methylation may be a biomarker during cervical carcinogenesis that might serve as an early indication of cervical cancer.

Highlights

Cervical cancer is the third most common cancer, after breast and colorectal cancer, among women worldwide, with 529,500 estimated new cases and 275,000 deaths in 2008 according to Ferlay et al [1]
Study search and selection criteria We systematically reviewed the studies of Death-associated protein kinase1 (DAPK1) promoter methylation in cervical cancer, and attempted to find the eligible studies within PubMed, EMBASE, Web of Science and CNKI, using various combinations of Medical Subject Headings (MeSH) and non-MeSH terms
The studies for inclusion in this meta-analysis had to meet the following standards: (i) the studies assessed the association of DAPK1 methylation and cervical cancer, (ii) the studies provided detailed information about the frequency of DAPK1 methylation for both the cancer group and the normal control group, (iii) methods for the detection of DAPK1 methylation were limited to the methylation-specific polymerase chain reaction (MSP) and real-time quantitative polymerase chain reaction (QMSP)

Summary

Introduction

Cervical cancer is the third most common cancer, after breast and colorectal cancer, among women worldwide, with 529,500 estimated new cases and 275,000 deaths in 2008 according to Ferlay et al [1]. Hypermethylation of the promoter regions of tumor suppressor genes can cause gene inactivation, which is important in the pathogenesis of cancers, and usually occurs in the early stages of cancer development in various types of cancer, including cervical cancer [4,5]. Because DAPK1 is an important tumor suppressor gene that has been studied extensively, we performed a meta-analysis to assess the association between DAPK1 promoter methylation and cervical cancer. Death-associated protein kinase (DAPK1) is an important tumor suppressor gene. DNA methylation can inactivate genes, which has often been observed in the carcinogenesis of cervical cancer. During the past several decades, many studies have explored the association between DAPK1 promoter methylation and cervical cancer. We conducted a metaanalysis to assess the association between DAPK1 promoter methylation and cervical cancer

Methods

Results

Conclusion