Abstract
BackgroundThe death-associated protein kinase (DAPK) is a tumor suppressor gene, which is a mediator of cell death of INF-γ–induced apoptosis. Aberrant methylation of DAPK promoter has been reported in patients with head and neck squamous cell carcinoma (HNSCC). However, the results of these studies are inconsistent. Hence, the present study aimed to evaluate the association between the promoter methylation of DAPK gene and HNSCC.MethodsRelevant studies were systematically searched in PubMed, Web of Science, Ovid, and Embase. The association between DAPK promoter methylation and HNSCC was assessed by odds ratio (ORs) and 95% confidence intervals (CI). To evaluate the potential sources of heterogeneity, we conducted the meta-regression analysis and subgroup analysis.ResultsEighteen studies were finally included in the meta-analysis. The frequency of DAPK promoter methylation in patients with HNSCC was 4.09-fold higher than the non-cancerous controls (OR = 3.96, 95%CI = 2.26–6.95). A significant association between DAPK promoter methylation and HNSCC was found among the Asian region and the Non-Asia region (Asian region, OR = 4.43, 95% CI = 2.29–8.58; Non-Asia region, OR = 3.39, 95% CI = 1.18–9.78). In the control source, the significant association between DAPK promoter methylation and HNSCC was seen among the autologous group and the heterogeneous group (autologous group, OR = 2.71, 95% CI = 1.49–4.93; heterogeneous group, OR = 9.50, 95% CI = 2.98–30.27). DAPK promoter methylation was significantly correlated with alcohol status (OR = 1.85, 95% CI = 1.07–3.21).ConclusionThe results of this meta-analysis suggested that aberrant methylation of DAPK promoter was associated with HNSCC.
Highlights
Head and neck squamous cell carcinoma(HNSCC)is the sixth most common cancer worldwide [1]
A significant association between death-associated protein kinase (DAPK) promoter methylation and head and neck squamous cell carcinoma (HNSCC) was found among the Asian region and the Non-Asia region (Asian region, odds ratio (OR) = 4.43, 95% confidence intervals (CI) = 2.29–8.58; Non-Asia region, OR = 3.39, 95% CI = 1.18–9.78)
The significant association between DAPK promoter methylation and HNSCC was seen among the autologous group and the heterogeneous group
Summary
Head and neck squamous cell carcinoma(HNSCC)is the sixth most common cancer worldwide [1]. The five-year survival of patients with HNSCC remains about 40–50% [2].The molecular mechanisms associated with the pathogenesis of HNSCC comprise of a variety of genetic alterations such as mutations and epigenetic modifications, including methylation of CpG islands. The epigenetic modification resulting in the alteration of expression of tumor-related genes is considered crucial in the development of HNSCC [3,4]. The methylation of DAPK promoter has been found to be an important epigenetic modification in several types of cancers [10–12]. The death-associated protein kinase (DAPK) is a tumor suppressor gene, which is a mediator of cell death of INF-γ–induced apoptosis. Aberrant methylation of DAPK promoter has been reported in patients with head and neck squamous cell carcinoma (HNSCC).
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