Association between promoter methylation of DAPK gene and HNSCC: A meta-analysis

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.

Hypermethylation status of DAPK, MGMT and RUNX3 in HPV negative oral and oropharyngeal squamous cell carcinoma

“…In relation to TSG DAPK , preview studies reveal that its hypermethylation is a common phenomenon in HNSCC ( Kulkarni and Saranath, 2004 ; Li et al , 2013 ; Misawa et al , 2016 ). It is known that DAPK , which is a mediator of cell death of interferon-gamma (INF-γ)-induced apoptosis ( Cai et al , 2017 ), is essential for activation of various cell death mechanisms, caspase dependent or not, and the p19ARF/p53 signaling pathway, a classic pathway in cell cycle control ( Bialik and Kimchi, 2004 ). Since death pathways abolition is critical for tumor growth, DAPK hypermethylation may be suggestive of a higher malignant potential.…”

miR-483-5p decreases the radiosensitivity of nasopharyngeal carcinoma cells by targeting DAPK1

“…Loss of DAPK1 expression occurs in a variety of cancers, mainly via methylation of its promoter. Loss of DAPK1 expression is a crucial role in tumor carcinogenesis and enhances the metastatic potential of cancer cells [20,21]. DAPK1 is down-regulated or absent in numerous malignant tumors, whereas the over-expression of DAPK1 can induce apoptosis in several cell lines [21,22].…”

Epigenetic Modifications in Head and Neck Cancer

“…Death-associated protein kinase (DAPK), a tumor suppressor gene, is also hypermethylated in head and neck cancer (Sanchez-Cespedes et al 2000; Choudhury and Ghosh 2015), and hypermethylation is positively correlated with LN metastases and with stages III and IV of HNSCC (Sanchez-Cespedes et al 2000), as well as inversely correlated with lower expression of DAPK in tongue cancer (Bhat et al 2017). A meta-analysis of eighteen studies confirmed that methylation of the DAPK promoter is over fourfold higher in HNSCC patients compared to healthy controls (Cai et al 2017), while another meta-analysis confirmed DAPK promoter hypermethylation among OSCC patients (Don et al 2014) as well as an association with a higher risk of nasopharyngeal carcinoma (Zhang et al 2018a). The DAPK promoter is also more highly methylated in OSCC samples compared to matched surgical margins, and interestingly is associated with LN metastasis and older age of HNSCC patients (Strzelczyk et al 2019).…”