ABSTRACT
Introduction: Gliomas are the most common primary tumors of the central nervous system. The majority are formed by glioblastomas, with high degrees of proliferation and invasion, with biological heterogeneity and little response to current treatments. Immunotherapy and genetherapy have not shown efficacy and, therefore, it is necessary to seek knowledge of new molecules and genes involved in their carcinogenesis. Objectives: To evaluate whether the alpha 5 gamma-aminobutyric acid receptor (GABRA5) is a potential therapeutic target or biomarker for gliomas of different subgroups, and the correlation between GABRA5 messenger ribonucleic acid (mRNA) levels and overall survival. Methods: Integrative review carried out on virtual platforms in Portuguese and English, carried out using descriptors related to the topic, described in DeCS as "glioma, central nervous system, glioblastoma, GABA, GABRA5" with AND or OR search, initially considering the title and/or summary. Afterwards, in those that were most related to the topic, the texts were read in full. Results: 36 articles were included. Conclusion: GABRA5 mRNA levels in glioma samples from all histological subgroups are lower compared to control. No correlation was observed between GABRA5 mRNA levels and overall survival in the evaluated subgroups.
Introdução: Gliomas são os tumores primários mais comuns do sistema nervoso central e a maioria é formada por glioblastomas, com graus elevados de proliferação e invasão, com heterogeneidade biológica e pouca resposta aos tratamentos atuais. Imunoterapia e geneterapia não têm mostrado eficácia e, por isso, é necessário buscar conhecimento de novas moléculas e genes envolvidos na sua carcinogênese. Objetivos: Avaliar se o receptor do ácido gama-aminobutírico alfa 5 (GABRA5) é potencial alvo terapêutico ou biomarcador para gliomas de diferentes subgrupos, e a correlação entre os níveis de ácido ribonucleico mensageiro (mRNA) de GABRA5 com a sobrevida global. Métodos: Revisão integrativa feita em plataformas virtuais, em português e inglês, realizada por descritores relacionados ao tema, descritos no DeCS como "glioma, sistema nervoso central, glioblastoma" com busca AND ou OR, considerando-se inicialmente o título e/ou resumo. Após, naqueles que tinham maior relação ao tema, foi realizada a leitura na íntegra dos textos. Resultados: Foram incluídos 36 artigos. Conclusão: Os níveis de mRNA de GABRA5 em amostras de gliomas de todos os subgrupos histológicos são menores, em comparação ao controle. Não foi observada correlação entre os níveis de mRNA de GABRA5 com a sobrevida global dos subgrupos avaliados.
ABSTRACT
Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABAA receptors. The GABRA5 gene, which encodes the α5 subunit of the GABAA receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABAA receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABAA 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 GABAA 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 GABAA receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABAA receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABAA receptors as a therapeutic target in glioma.
