Open Access

Identification of aberrantly methylated differentially expressed genes in glioblastoma multiforme and their association with patient survival

  • Authors:
    • Miao Zhang
    • Xintong Lv
    • Yuanjun Jiang
    • Guang Li
    • Qiao Qiao
  • View Affiliations

  • Published online on: July 24, 2019     https://doi.org/10.3892/etm.2019.7807
  • Pages: 2140-2152
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioblastoma multiforme (GBM) is the most malignant primary tumour type of the central nervous system with limited therapeutic options and poor prognosis, and its pathogenic mechanisms have remained to be fully elucidated. Aberrant DNA methylation is involved in multiple biological processes and may contribute to the occurrence and development of GBM by affecting the expression of certain genes. However, the specific molecular mechanisms remain to be fully elucidated. The present study focused on uncovering differentially expressed genes with altered methylation status in GBM and aimed to discover novel biomarkers for the diagnosis and treatment of GBM. These genes were identified by combined analysis of multiple gene expression and methylation datasets from gene expression omnibus (GSE16011, GSE50161 and GSE 50923) to increase the reliability. In addition, The Cancer Genome Atlas (TCGA) dataset for GBM was used to test the stability of the results. Overall, 251 hypomethylated upregulated genes (Hypo‑UGs) and 199 hypermethylated downregulated genes (Hyper‑DGs) were identified in the present study. Functional enrichment analysis revealed that the Hypo‑UGs are involved in the regulation of immune‑ and infection‑associated signalling, while the Hyper‑DGs are involved in the regulation of synaptic transmission. The three hub genes for Hyper‑DGs (somatostatin, neuropeptide Y and adenylate cyclase 2) and five hub genes for Hypo‑UGs [interleukin‑8, matrix metalloproteinase (MMP)9, cyclin‑dependent kinase 1, 2'‑5'‑oligoadenylate synthetase 1, C‑X‑C motif chemokine ligand 10 and MMP2] were identified by protein‑protein interaction network analysis. Among the Hypo‑UGs and Hyper‑DGs, overexpression of C‑type lectin domain containing 5A, epithelial membrane protein 3, solute carrier family 43 member 3, STEAP3 metalloreductase, tumour necrosis factor α‑induced protein 6 and apolipoprotein B mRNA editing enzyme catalytic subunit 3G was significantly associated with poor prognosis in the TCGA and GSE16011 datasets (P<0.001). In conclusion, the present study uncovered numerous novel aberrantly methylated genes and pathways associated with GBM. Methylation‑based markers, including the hub genes and prognostic genes identified, may potentially serve as markers for the diagnosis of GBM and targets for its treatment.

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September 2019
Volume 18 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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APA
Zhang, M., Lv, X., Jiang, Y., Li, G., & Qiao, Q. (2019). Identification of aberrantly methylated differentially expressed genes in glioblastoma multiforme and their association with patient survival. Experimental and Therapeutic Medicine, 18, 2140-2152. https://doi.org/10.3892/etm.2019.7807
MLA
Zhang, M., Lv, X., Jiang, Y., Li, G., Qiao, Q."Identification of aberrantly methylated differentially expressed genes in glioblastoma multiforme and their association with patient survival". Experimental and Therapeutic Medicine 18.3 (2019): 2140-2152.
Chicago
Zhang, M., Lv, X., Jiang, Y., Li, G., Qiao, Q."Identification of aberrantly methylated differentially expressed genes in glioblastoma multiforme and their association with patient survival". Experimental and Therapeutic Medicine 18, no. 3 (2019): 2140-2152. https://doi.org/10.3892/etm.2019.7807