E- ISSN: 3023-6215
Comparative Transcriptome Analysis Identifies Target Genes for Treatment of IDH Wild-type Lower-grade Gliomas [Anatol J Med ]
Anatol J Med . 2023; 33(1): 100-119 | DOI: 10.4274/terh.galenos.2023.60024

Comparative Transcriptome Analysis Identifies Target Genes for Treatment of IDH Wild-type Lower-grade Gliomas

Fadime Öztoprak1, Zerrin Işık2, Yavuz Oktay3
1Dokuz Eylül University, İzmir International Biomedicine and Genome Institute, İzmir, Turkey
2Dokuz Eylül University Faculty of Engineering, Computer Engineering Department, İzmir, Turkey
3İzmir Biomedicine and Genome Center, İzmir, Turkey and Dokuz Eylül University Faculty of Medicine, Department of Medical Biology, İzmir, Turkey

Objective: Isocitrate dehydrogenase 1/2 (IDH 1/2) mutations define a group of low-grade gliomas (LGGs) that display more favorable prognosis compared with LGGs without them. Although IDH wild-type (IDHwt) LGGs are classified as low-grade, they almost invariably progress to higher grades and rarely respond to aggressive treatment regimes. Here, we employed a comparative transcriptomic approach to identify key genes that could significantly contribute to the aggressive progression of IDHwt LGGs.
Methods: Using The Cancer Genome Atlas LGG cohort data and weighted gene coexpression network analysis methodology, we identified modules that correlated significantly with clinical features. We focused on modules that correlated with telomerase reverse transcriptase (TERT) promoter mutation status, as TERT promoter mutations are shared between glioblastomas and oligodendrogliomas, however, with two opposite prognostic outcomes. We selected module pathways shared between IDH mutant (IDHmt) and IDHwt LGGs and identified genes that were differentially expressed between the two groups.
Results: Several synaptic proteins are down-regulated in IDHwt compared with IDHmt, while GNG12 and VIPR2 are up-regulated. Finally, we identified known drugs that could target many of those genes and therefore could be tested against IDHwt LGGs.
Conclusion: Targeting of multiple candidate genes identified in this study could provide novel approaches toward the treatment of IDHwt LGGs.

Keywords: Low-grade gliomas, IDH 1, differential gene expression analysis, weighted gene co-expression network analysis, therapeutic target

Corresponding Author: Yavuz Oktay, Türkiye
Manuscript Language: English
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