Gene Expression of GABA_A Receptor Subunits and Association with Patient Survival in Glioma

Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABA_A receptors. The GABRA5 gene, which encodes the α5 subunit of the GABA_A receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABA_A receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABA_A receptor subunits in different types of glioma, and its possible association with patient prognosis assessed by overall survival (OS). Data were obtained from the French and The Cancer Genome Atlas Brain Lower Grade Glioma (TCGA-LGG) datasets and analyzed for expression of GABA_A receptor subunit genes. OS was calculated using the Kaplan-Meier estimate. We found that genes GABRA2, GABRA3, GABRB3, GABRG1, and GABRG2 showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of GABRA2 was associated with shorter OS, whereas, in contrast, higher levels of GABRB3 were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, GABRA3, GABRB3, GABRG1, and GABRG2, were associated with longer OS. High GABRB3 expression was related to longer survival when low grade glioma types were analyzed separately. Our results suggest an overall association between higher expression of most genes encoding GABA_A receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABA_A receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABA_A receptors as a therapeutic target in glioma.