Identification of potential therapeutic targets for gliomas by bioinformatics analysis

Oncol Lett. 2017 Nov;14(5):5203-5210. doi: 10.3892/ol.2017.6850. Epub 2017 Aug 28.

Abstract

Gliomas are primary tumors that originate in the brain or spinal cord and develop from supportive glial cells. The present study aimed to identify potential candidate molecular markers for the treatment of gliomas, and to explore the underlying mechanisms of this disease. The gene expression profile data GSE50021, which consisted of 10 specimens of normal brain tissues and 35 specimens of glioma tissues, was downloaded from Gene Expression Omnibus (GEO). The methylation microarray data GSE50022, consisting of 28 glioma specimens, was also downloaded from GEO. Differentially expressed genes (DEGs) between patients with glioma and normal individuals were identified, and key methylation sites were screened. Transcriptional regulatory networks were constructed, and target genes were selected. Survival analysis of key methylation sites and risk analysis of sub-pathways were performed, from which key genes and pathways were selected. A total of 79 DEGs and 179 key methylation sites were identified, of which 20 target genes and 36 transcription factors were included in the transcriptional regulatory network. Glutamate metabotropic receptor 2 (GRM2) was regulated by 8 transcription factors. Inositol-trisphosphate 3-kinase A (ITPKA) was a significantly enriched DEG, associated with the inositol phosphate metabolism pathway, Survival analysis revealed that the survival time of patients with lower methylation levels in cg00157228 was longer than patients with higher methylation levels. ITPKA was the closest located gene to cg00157228. In conclusion, GRM2 and enriched ITPKA, associated with the inositol phosphate metabolism pathway, may be key mechanisms in the development and progression of gliomas. Furthermore, the present study provided evidence for an additional mechanism of methylation-induced gliomas, in which methylation results in the dysregulation of specific transcripts. The results of the present study may provide a research direction for studying the mechanisms underlying the development and progression of gliomas.

Keywords: gliomas; methylation; sub-pathway.