DNA methylation profiling identifies potentially significant epigenetically‑regulated genes in glioblastoma multiforme

Abstract

Glioblastoma multiforme (GBM) is one of the most lethal and damaging types of human cancer. The current study was conducted to identify differentially methylated genes (DMGs) between GBM and normal controls, and to improve our understanding of GBM at the epigenetic level. The DNA methylation profile of GBM was downloaded from the Gene Expression Omnibus (GEO) database using the accession number GSE50923. The MethyAnalysis package was applied to identify DMGs between GBM and controls, which were then analyzed by functional enrichment analysis. Protein-protein interaction (PPI) networks were constructed using the hypermethylated and hypomethylated genes. Finally, transcription factors (TFs) that can regulate the hypermethylated and hypomethylated genes were predicted, followed by construction of transcriptional regulatory networks. Furthermore, another relevant dataset, GSE22867, was downloaded from the GEO database for data validation. A total of 476 hypermethylated and 850 hypomethylated genes were identified, which were mainly associated with the functions of ‘G-protein-coupled receptors ligand binding’, ‘cytokine activity’, ‘cytokine-cytokine receptor interaction’, and ‘D-glutamine and D-glutamate metabolism’. The hypermethylated gene neuropeptide Y ( NPY ) and the hypomethylated gene tumor necrosis factor ( TNF ) demonstrated high degrees in the PPI network. Forkhead box protein A1 ( FOXA1 ), potassium voltage-gated channel subfamily C member 3 ( KCNC3 ) and caspase-8 ( CASP8 ) exhibited high degrees in the transcriptional regulatory networks. In addition, the methylation profiles of NPY, TNF, FOXA1, KCNC3 and CASP8 were confirmed by another dataset. In summary, the present study systematically analyzed the DNA methylation profile of GBM using bioinformatics approaches and identified several abnormally methylated genes, providing insight into the molecular mechanism underlying GBM.

FAM72, Glioblastoma Multiforme (GBM) and Beyond

“…This probably also works for the other FAM72 member expressions such as FAM72A, FAM72B, and FAM72C (due to high homology (99%) in amino acid sequences) [ 25 ]. As for GBM, Kan et al could not identify epigenetically affected FAM72, though our data showed a change in the methylation status ( Figure 8 ) [ 12 , 135 ].…”

“…However, in non-neuronal cells, SRGAP2 expression is needed for rearranging the cytoskeleton required for cell-specific locomotion and motility and, if genomic rearranging occurs within the genomic SRGAP2 body, its tumor suppressor function is abolished, and metastasis is induced [ 26 , 132 , 133 , 134 ]. Overall, however, it appears that in cancer tissues including GBM [ 135 ], the methylation status does not have a major impact on the |-SRGAP2–FAM72-| master gene.…”

Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance

“…[68] DNA hypo-and hypermethylation of critical genes is also associated with malignant transformation of brain tumors. [69,70] Accumulating evidence suggests that PMT regulation by epigenetic controlled DNA methylation is associated with glioma progression. [71] Zinc finger and BTB domain containing 18 (ZBTB18) gene is a transcriptional tumor suppressor associated with brain development and neuronal differentiation.…”

Potential Molecular Mechanism of TNF Superfamily-Related Genes in Glioblastoma Multiforme Based on Transcriptome and Epigenome

“…GBM is the most common malignant brain tumor in adults ( 34 ). Although TNF and methylation sites are proved to be associated with the progression of disease ( 35 ), the detailed mechanisms are still unclear. In this study, the bioinformatics analysis showed that there were 41 DEGs between two groups.…”