High Expression of GABAA 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_A) receptor, which is a ligand-gated ion channel. GABA_A receptor activation via GABA binding allows for an intracellular influx of Cl^- ions, thus inducing cellular hyperpolarization. Each GABA_A 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_A 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_A receptor β subunits with MB patients' overall survival (OS). <b>Methods:</b> The expression of genes encoding GABA_A 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_A receptors containing β subunits in influencing MB progression.