Prognostic significance of DAPK promoter methylation in lymphoma: A meta-analysis

Abstract

We aimed to characterize the clinical significance of epigenetic loss of death-associated protein kinase (DAPK) gene function through promoter methylation in the development and prognosis of lymphoma. PubMed, Web of Science and ProQuest databases were searched for relevant studies. Twelve studies involving 709 patients with lymphoma were identified. The prognostic value of DAPK methylation was expressed as risk ratio (RR) and its corresponding 95% confidence interval (CI), while the associations between DAPK methylation and the clinical characteristics of patients with lymphoma were expressed as odd ratios (ORs) and their corresponding 95% CIs. Meta-analysis showed that the 5-year survival rate was significantly lower in lymphoma patients with hypermethylated DAPK (RR = 0.85, 95% CI (0.73, 0.98), P = 0.025). Sensitivity analysis demonstrated consistent result. However, no associations were found between DAPK methylation and clinicopathological features of lymphoma, in relation to gender (OR = 1.07, 95% CI (0.72, 1.59), P = 0.751), age (OR = 1.01, 95% CI (0.66, 1.55), P = 0.974), international prognostic index (OR = 1.20, 95% CI (0.63, 2.27), P = 0.575), B symptoms (OR = 0.76, 95% CI (0.38, 1.51), P = 0.452), serum lactate dehydrogenase (OR = 1.13, 95% CI (0.62, 2.05), P = 0.683), and BCL-2 expression (OR = 1.55, 95% CI (0.91, 2.66), P = 0.106). Lymphoma patients with hypermethylated DAPK are at risk for poorer 5-year survival rate. DAPK methylation may serve as a negative prognostic biomarker among lymphoma patients, although it may not be associated with the progression of lymphoma.

Can peripheral blood provide good DNA methylation biomarkers in myelodysplastic syndrome?

“…In hematological cancers such as monoclonal gammopathies, it was observed that DAPK methylation might be a marker of disease progression with a negative impact on disease prognosis [39]. A more recent study in lymphoma patients also demonstrated that DAPK promoter methylation might serve as a negative prognostic biomarker even though it is not associated with lymphoma progression [40]. Despite the impact of DNA methylation in several neoplasias, it is important to point out that there is also a link between DNA methylation and aging, showing the establishment of global hypomethylation and regions of CpG-island methylation with age [41].…”

KLF4, DAPK1 and SPG20 promoter methylation is not affected by DNMT1 silencing and hypomethylating drugs in lymphoma cells

“…DAPK1 plays a role in lymphomas, as recently demonstrated by a meta-analysis where hypermethylation of the promoter was found to be associated with the 5-year survival rate of patients ( 8 , 9 ). Overall, DAPK1 hypermethylation corresponds to a significantly lower survival and represents an independent, negative prognostic biomarker ( 8 ).…”

“…Hypermethylated KLF4 has also been associated with the poor prognosis of patients with splenic marginal zone lymphomas (SMZL) and SMZL cell lines exposed to hypomethylating agents show a reduced proliferation (6,7). DAPK1 plays a role in lymphomas, as recently demonstrated by a meta-analysis where hypermethylation of the promoter was found to be associated with the 5-year survival rate of patients (8,9). Overall, DAPK1 hypermethylation corresponds to a significantly lower survival and represents an independent, negative prognostic biomarker (8).…”

“…A meta-analysis recently published on patients with lymphoma evidenced how the hypermethylation of DAPK1 tumor suppressor represents an independent prognostic biomarker for the 5-year survival of patients ( 8 ). DAPK1 promoter methylation has been shown to be methylated in a significant proportion of lymphomas including FL, mucosa-associated lymphoid tissue and DLBCL ( 4 , 34 ).…”

Retraction: Prognostic significance of DAPK promoter methylation in lymphoma: A meta-analysis

“…In light of these issues, PLOS ONE cannot stand by the reliability of the reported research, and the PLOS ONE Editors retract this article [ 1 ].…”