High Expression of GABA_A Receptor β Subunit Genes Is Associated with Longer Overall Survival in Medulloblastoma

Background/Objectives: 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 GABRB1, GABRB2, and GABRB3, 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). Methods: 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. Results: High GABRB1 expression was associated with better OS within each of the four molecular subgroups. The GABRB2 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. GABRB3 expression was significantly higher in Group 3 and Group 4 MB, and high expression of GABRB3 genes was associated with longer OS in the sonic hedgehog (SHH) subgroup. The high expression of GABRB1, GABRB2, and GABRB3 is associated with longer patient OS in a subgroup-specific manner. Conclusions: These results indicate a role for GABA_A receptors containing β subunits in influencing MB progression.