Association between DAPK1 Promoter Methylation and Cervical Cancer: A Meta-Analysis

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.

Identification of Frequent Promoter Methylation of Death-Associated Protein Kinase in Liquid-Based Papanicolaous Test Samples in Vietnamese Population

“…In addition to HPV infection, particularly high-risk HPV genotypes, recently, the inactivation of TSGs due to promoter hypermethylation has been reported that it is a frequent mechanism plays an important criterion in cervical carcinogenesis [8,[14][15][16]. In this study, we demonstrated that the hypermethylation of the DAPK gene promoter was found in high frequency in high-risk HPV infected samples, counting for 66.67% (24 of 36 samples), compared to low-risk HPV infected samples, counting for 12.0% (3 of 25 samples) and non-HPV infected samples, counting for 2.08% (1of 48 samples).…”

“…Additional genetic and epigenetic alterations are required for progression from precancerous disease to invasive cancer [8,12,13]. Among the putative molecular alterations involved in cervical carcinogenesis process, promoter hypermethylation, an important epigenetic modification, has long been found to be a major mechanism of inactivation of tumor suppressor genes (TSGs), which has been considered as an early epigenetic event in driving carcinogenesis of many human cancers, including cancer of cervix [14][15][16].…”

“…The death-associated protein kinase (DAPK), a member of TSG family, located at 9q21.33, was a calcium/calmodulin-dependent seurine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy [14][15][16][17][18]. DAPK has been proved as participating in interferon-γ, Fas, tumor necrosis factor-β, extracellular signal-regulated kinase, C-myc and E2F-induced apoptosis, which suggested that DAPK is a conjunction of all kinds of apoptosis signals [18,19].…”

“…DAPK has been proved as participating in interferon-γ, Fas, tumor necrosis factor-β, extracellular signal-regulated kinase, C-myc and E2F-induced apoptosis, which suggested that DAPK is a conjunction of all kinds of apoptosis signals [18,19]. DAPK promoter aberrant hypermethylation has been reported involving in many primary tumors, including cervical carcinoma [16,17]. In Vietnam, the studies revealed to evaluation of TSGs had been reported, but still limited.…”

Recent Progress in Triple Negative Breast Cancer Research

“…In cervical cancer, the frequencies of DAPK1 promoter hypermethylation ranges from 30.0% to 78.6% (median, 59.3%) and is more pronounced in more advanced stages (Narayan et al, 2003). It can then be regarded as a valuable biomarker for cervical cancer development (Xiong et al, 2014).…”