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

Most of the rapid inhibitory neurotransmission in the brain is mediated through activation of the γ-aminobutyric acid (GABA) type A (GABA) receptor, which is a ligand-gated ion channel. GABA receptor activation via GABA binding allows for an intracellular influx of Cl ions, thus inducing cellular hyperpolarization. Each GABA 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 receptor, namely , , and , 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 receptor β subunits with MB patients' overall survival (OS). The expression of genes encoding GABA 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. High expression was associated with better OS within each of the four molecular subgroups. The 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. expression was significantly higher in Group 3 and Group 4 MB, and high expression of genes was associated with longer OS in the sonic hedgehog (SHH) subgroup. The high expression of , , and is associated with longer patient OS in a subgroup-specific manner. These results indicate a role for GABA receptors containing β subunits in influencing MB progression.