10211- GEN-12 IDENTIFICATION OF PROGNOSIS-RELATED METHYLATION PROFILES AND METHYLATION BIOMARKERS IN IDH-WILD-TYPE GLIOBLASTOMA

Abstract BACKGROUND Genome-wide DNA methylation analysis is currently available and is used to diagnose brain tumors. Although MGMT promoter hypermethylation is a strong biomarker in glioblastoma (GBM), there are few reports of DNA methylation profiles associated with prognosis or other DNA methylation biomarkers. In this study, we examined DNA methylation profiles correlated with prognosis and DNA methylation biomarkers. METHODS We selected 20 long-term survivors (LS) and 20 short-term survivors (SS) from 407 patients with newly diagnosed IDH-wild-type GBM treated at our institution, divided by MGMT methylation status (methylated; M/unmethylated; U), and adjusted for age. DNA methylation analysis was performed by EPIC array, and DKFZ classifier, tSNE analysis, and copy number analysis were performed. DNA methylation data and DNA methylation profiles were compared between LS and SS groups. RESULTS There were no significant differences in age and sex between the LS and SS groups in the M and U groups, respectively. Median OS (months) in the M group was 62.1/17.3 in LS/SS and 28.1/6.8 in the U group. Differentially methylated genes in the promoter region between LS/SS groups in the M group were HOXD13 and HAGH (methylated in LS), KCTD14 and ALPK3 (methylated in SS). Those in the U group were KLF14 and HOXB4 (methylated in LS), ZMYND10 and SLFN13 (methylated in SS). Gene Ontology analysis revealed that the genes with a hypermethylated promoter in the LS are enriched in G protein-coupled receptor signaling pathway and plasma membrane in the M group and Homeobox antennapedia and sequence-specific double-stranded DNA binding in the U group. CONCLUSION We identified DNA methylation biomarkers and key pathways involved in the prognosis of GBM with methylated and unmethylated MGMT promoter. Multi-omics analysis is necessary to validate the mechanism related to the prognosis of GBM.