High Expression of GABA<sub>A</sub> Receptor β Subunit Genes Is Associated with Longer Overall Survival in Medulloblastoma
<b>Background/Objectives:</b> Most of the rapid inhibitory neurotransmission in the brain is mediated through activation of the γ-aminobutyric acid (GABA) type A (GABA<sub>A</sub>) receptor, which is a ligand-gated ion channel. GABA<sub>A</sub> receptor activation...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
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| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3425/14/11/1146 |
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| Summary: | <b>Background/Objectives:</b> Most of the rapid inhibitory neurotransmission in the brain is mediated through activation of the γ-aminobutyric acid (GABA) type A (GABA<sub>A</sub>) receptor, which is a ligand-gated ion channel. GABA<sub>A</sub> receptor activation via GABA binding allows for an intracellular influx of Cl<sup>−</sup> ions, thus inducing cellular hyperpolarization. Each GABA<sub>A</sub> receptor consists of a combination of five subunits, and several subunits have been proposed as biomarkers and therapeutic targets in cancer. Here, we show the expression of genes encoding β subunits of the GABA<sub>A</sub> receptor, namely <i>GABRB1</i>, <i>GABRB2</i>, and <i>GABRB3</i>, across the four different molecular subgroups of medulloblastoma (MB), which is the most common malignant pediatric brain tumor. We also show the associations of GABA<sub>A</sub> receptor β subunits with MB patients’ overall survival (OS). <b>Methods:</b> The expression of genes encoding GABA<sub>A</sub> receptor β subunits was analyzed using a previously described dataset comprising 763 MB tumor samples. Patients were classified into high- and low-gene-expression groups, and the Kaplan–Meier estimate was used to examine the relationship between gene expression levels and patient OS. <b>Results:</b> High <i>GABRB1</i> expression was associated with better OS within each of the four molecular subgroups. The <i>GABRB2</i> gene showed higher transcript levels in Group 3 MB compared to all other subgroups, and high expression was associated with better prognosis in Group 3 tumors. <i>GABRB3</i> expression was significantly higher in Group 3 and Group 4 MB, and high expression of <i>GABRB3</i> genes was associated with longer OS in the sonic hedgehog (SHH) subgroup. The high expression of <i>GABRB1</i>, <i>GABRB2</i>, and <i>GABRB3</i> is associated with longer patient OS in a subgroup-specific manner. <b>Conclusions:</b> These results indicate a role for GABA<sub>A</sub> receptors containing β subunits in influencing MB progression. |
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| ISSN: | 2076-3425 |