The prognostic value of DAPK1 hypermethylation in gliomas: A site-specific analysis

Abstract

Background and aims: The gene of death associated protein kinase 1 (DAPK1) has been reported to be methylated in various cancers including gliomas. However, its prognostic value for gliomas is still controversy, and the methylation at specific CpG sites of DAPK1 has not been investigated. The aim of this study was to prognostically evaluate the methylation level of different CpG sites within DAPK1 promoter region in gliomas.

Methods: Based on sodium bisulfite treated DNA products, we made use of DNA pyrosequencing method to evaluate overall and site-specific methylation of DAPK1 in 143 gliomas and 26 benign tumors (meningeomas) or normal brain tissues. We both statistically analyzed the association between methylation levels of each CpG site and the clinicopathological characteristics, and estimated the prognosis predictive value of site-specific methylation for glioma patients.

Results: Methylation status of DAPK1 site -1527, -1543, and the overall five sites concerned was higher in gliomas than controlled subjects (p < 0.001). Hypermethylation at site -1527 or together with site -1543 associated with better survival in patients taken postoperative therapies (-1527: p = 0.002; -1527 & -1543: p = 0.023), as well as in patients just underwent radiotherapy after surgery (-1527: p = 0.015; -1527 & -1543: p = 0.030). However, Cox regression analysis indicated the site-specific methylation was not independent contributor for gliomas prognosis.

Conclusion: Analysis of DAPK1 gene promoter by quantitative pyrosequencing provided more detailed information of methylation status of CpG sites. DAPK1 methylation level is associated with gliomas clinical features and outcomes. Interestingly, the hypermethylation at site -1527 or together with site -1543 indicated good sensitivity of postoperative therapies, especially radiotherapy. Thus, site specifically analysis of DAPK1 methylation may be a valuable diagnostic and prognostic estimation for gliomas.

Keywords: Death associated protein kinase 1 (DAPK1); Gliomas; Pyrosequencing; Site-specific methylation.