Clinical significance of DAPK promoter hypermethylation in gastric cancer: a meta-analysis

Death-associated protein kinase (DAPK) gene promoter methylation was reported to be associated with gastric cancer (GC) in previous studies. However, the results remained inconsistent. We conducted a systematic literature search of the Embase, PubMed, Cochrane Library, Web of Science, and Chinese Biomedical Database for the relevant articles (up to October 2015). Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the strength of the association between DAPK methylation and GC risk. A total of 24 studies, comprising 3,250 samples, were analyzed in this meta-analysis. Our study revealed that DAPK promoter methylation levels were significantly different in the following comparisons: GC tissues vs. adjacent tissues (OR = 3.29, 95% CI = 1.48-7.33, P = 0.004), GC tissues vs. normal tissues (OR = 19.91, 95% CI = 11.77-33.69, P< 0.001), GC blood samples vs. normal blood samples (OR = 25.11, 95% CI = 3.48-181.36, P = 0.001), adjacent tissues vs. normal tissues (OR = 5.67, 95% CI = 3.95-8.12, P< 0.001), GC tissues vs. intestinal metaplasia (IM) tissues (OR = 3.29, 95% CI = 1.22-8.86, P = 0.019), IM tissues vs. normal tissues (OR = 8.01, 95% CI = 1.34-47.78, P = 0.022). In addition, the relationships between DAPK promoter methylation and TNM stage, differentiation status and nodal metastasis among GC cases were also identified. Our meta-analysis identified a strong association of DAPK promoter hypermethylation with GC risk, provided the evidence that DAPK promoter methylation might contribute to tumorigenesis, progression in GC, and might be a promising potential biomarker.