Dataset Information

Deciphering of Adult Glioma Vulnerabilities through Expression Pattern Analysis of GABA, Glutamate and Calcium Neurotransmitter Genes.

ABSTRACT: Adult infiltrating gliomas are highly aggressive tumors of the central nervous system with a dismal prognosis despite intensive multimodal therapy (chemotherapy and/or radiotherapy). In this study, we studied the expression, methylation and interacting miRNA profiles of GABA-, glutamate- and calcium-related genes in 661 adult infiltrating gliomas available through the TCGA database. Neurotransmitter-based unsupervised clustering identified three established glioma molecular subgroups that parallel major World Health Organization glioma subclasses (IDH-wildtype astrocytomas, IDH-mutant astrocytomas, IDH-mutant oligodendroglioma). In addition, this analysis also defined a novel, neurotransmitter-related glioma subgroup (NT-1), mostly comprised of IDH-mutated gliomas and characterized by the overexpression of neurotransmitter-related genes. Lower expression of neurotransmission-related genes was correlated with increased aggressivity in hypomethylated IDH-wildtype tumors. There were also significant differences in the composition of the tumor inflammatory microenvironment between neurotransmission-based tumor categories, with lower estimated pools of M2-phenotype macrophages in NT-1 gliomas. This multi-omics analysis of the neurotransmission expression landscape of TCGA gliomas-which highlights the existence of neurotransmission-based glioma categories with different expression, epigenetic and inflammatory profiles-supports the existence of operational neurotransmitter signaling pathways in adult gliomas. These findings could shed new light on potential vulnerabilities to exploit in future glioma-targeting drug therapies.

SUBMITTER: Nguyen HD

PROVIDER: S-EPMC9030730 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Deciphering of Adult Glioma Vulnerabilities through Expression Pattern Analysis of GABA, Glutamate and Calcium Neurotransmitter Genes.

Nguyen Hoang Dong HD Diamandis Phedias P Scott Michelle S MS Richer Maxime M

Journal of personalized medicine 20220414 4

Adult infiltrating gliomas are highly aggressive tumors of the central nervous system with a dismal prognosis despite intensive multimodal therapy (chemotherapy and/or radiotherapy). In this study, we studied the expression, methylation and interacting miRNA profiles of GABA-, glutamate- and calcium-related genes in 661 adult infiltrating gliomas available through the TCGA database. Neurotransmitter-based unsupervised clustering identified three established glioma molecular subgroups that parall ...[more]

PMID: 35455749

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Project description:Brain tumors, particularly high-grade glioblastomas, are a crucial public health issue due to poor prognosis and an extremely low survival rate. The glioblastoma multiforme (GBM) grows rapidly within its unique microenvironment that is characterized by active neural communications. Therefore, diverse neurotransmitters not only maintain normal brain functions but also influence glioma progression. To fully appreciate the relationship between neurotransmitters and glioma progression, we reviewed potential neurotransmitter contributors in human GBM and the much less aggressive Low-grade glioma (LGG) by combining previously published data from gene-mutation/mRNA sequencing databases together with protein-protein interaction (PPI) network analysis results. The summarized results indicate that glutamatergic and calcium signaling may provide positive feedback to promote glioma formation through 1) metabolic reprogramming and genetic switching to accelerate glioma duplication and progression; 2) upregulation of cytoskeleton proteins and elevation of intracellular Ca2+ levels to increase glutamate release and facilitate formation of synaptic-like connections with surrounding cells in their microenvironment. The upregulated glutamatergic neuronal activities in turn stimulate glioma growth and signaling. Importantly, the enhanced electrical and molecular signals from both neurons and glia propagate out to enable glioma symptoms such as epilepsy and migraine. The elevated intracellular Ca2+ also activates nitric oxide synthase to produce nitric oxide (NO) that can either promote or inhibit tumorigenesis. By analyzing the network effects for complex interaction among neurotransmitters such as glutamate, Ca2+ and NO in brain tumor progression, especially GBM, we identified the glutamatergic signaling as the potential therapeutic targets and suggest manipulation of glutamatergic signaling may be an effective treatment strategy for this aggressive brain cancer.

Dataset Information

Deciphering of Adult Glioma Vulnerabilities through Expression Pattern Analysis of GABA, Glutamate and Calcium Neurotransmitter Genes.

Publications

Deciphering of Adult Glioma Vulnerabilities through Expression Pattern Analysis of GABA, Glutamate and Calcium Neurotransmitter Genes.

Similar Datasets

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