Gene Expression of GABA<sub>A</sub> 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<sub>A</sub> receptors. The <i>GABRA5</i> gene, which encodes the α5 subunit of the GABA<sub>A</sub> receptor, has been implicated in an aggressive subgroup of medul...
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MDPI AG
2024-03-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/14/3/275 |
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| author | Rafael Badalotti Matheus Dalmolin Osvaldo Malafaia Jurandir M. Ribas Filho Rafael Roesler Marcelo A. C. Fernandes Gustavo R. Isolan |
| author_facet | Rafael Badalotti Matheus Dalmolin Osvaldo Malafaia Jurandir M. Ribas Filho Rafael Roesler Marcelo A. C. Fernandes Gustavo R. Isolan |
| author_sort | Rafael Badalotti |
| collection | DOAJ |
| description | Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABA<sub>A</sub> receptors. The <i>GABRA5</i> gene, which encodes the α5 subunit of the GABA<sub>A</sub> receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABA<sub>A</sub> receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABA<sub>A</sub> 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<sub>A</sub> receptor subunit genes. OS was calculated using the Kaplan–Meier estimate. We found that genes <i>GABRA2</i>, <i>GABRA3</i>, <i>GABRB3</i>, <i>GABRG1</i>, and <i>GABRG2</i> showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of <i>GABRA2</i> was associated with shorter OS, whereas, in contrast, higher levels of <i>GABRB3</i> were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, <i>GABRA3</i>, <i>GABRB3</i>, <i>GABRG1</i>, and <i>GABRG2</i>, were associated with longer OS. High <i>GABRB3</i> 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<sub>A</sub> receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABA<sub>A</sub> receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABA<sub>A</sub> receptors as a therapeutic target in glioma. |
| first_indexed | 2024-04-24T18:29:09Z |
| format | Article |
| id | doaj.art-7c6517376ccb45e79111004727b2b92e |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-04-24T18:29:09Z |
| publishDate | 2024-03-01 |
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| spelling | doaj.art-7c6517376ccb45e79111004727b2b92e2024-03-27T13:28:50ZengMDPI AGBrain Sciences2076-34252024-03-0114327510.3390/brainsci14030275Gene Expression of GABA<sub>A</sub> Receptor Subunits and Association with Patient Survival in GliomaRafael Badalotti0Matheus Dalmolin1Osvaldo Malafaia2Jurandir M. Ribas Filho3Rafael Roesler4Marcelo A. C. Fernandes5Gustavo R. Isolan6Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba 80730-000, BrazilInovAI Lab, nPITI/IMD, Federal University of Rio Grande do Norte, Natal 59078-970, BrazilGraduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba 80730-000, BrazilGraduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba 80730-000, BrazilDepartment of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, BrazilInovAI Lab, nPITI/IMD, Federal University of Rio Grande do Norte, Natal 59078-970, BrazilGraduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba 80730-000, BrazilRapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABA<sub>A</sub> receptors. The <i>GABRA5</i> gene, which encodes the α5 subunit of the GABA<sub>A</sub> receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABA<sub>A</sub> receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABA<sub>A</sub> 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<sub>A</sub> receptor subunit genes. OS was calculated using the Kaplan–Meier estimate. We found that genes <i>GABRA2</i>, <i>GABRA3</i>, <i>GABRB3</i>, <i>GABRG1</i>, and <i>GABRG2</i> showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of <i>GABRA2</i> was associated with shorter OS, whereas, in contrast, higher levels of <i>GABRB3</i> were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, <i>GABRA3</i>, <i>GABRB3</i>, <i>GABRG1</i>, and <i>GABRG2</i>, were associated with longer OS. High <i>GABRB3</i> 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<sub>A</sub> receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABA<sub>A</sub> receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABA<sub>A</sub> receptors as a therapeutic target in glioma.https://www.mdpi.com/2076-3425/14/3/275GABA<sub>A</sub> receptor subunit geneGABA<sub>A</sub> receptorgliomaglioblastomabrain tumor |
| spellingShingle | Rafael Badalotti Matheus Dalmolin Osvaldo Malafaia Jurandir M. Ribas Filho Rafael Roesler Marcelo A. C. Fernandes Gustavo R. Isolan Gene Expression of GABA<sub>A</sub> Receptor Subunits and Association with Patient Survival in Glioma Brain Sciences GABA<sub>A</sub> receptor subunit gene GABA<sub>A</sub> receptor glioma glioblastoma brain tumor |
| title | Gene Expression of GABA<sub>A</sub> Receptor Subunits and Association with Patient Survival in Glioma |
| title_full | Gene Expression of GABA<sub>A</sub> Receptor Subunits and Association with Patient Survival in Glioma |
| title_fullStr | Gene Expression of GABA<sub>A</sub> Receptor Subunits and Association with Patient Survival in Glioma |
| title_full_unstemmed | Gene Expression of GABA<sub>A</sub> Receptor Subunits and Association with Patient Survival in Glioma |
| title_short | Gene Expression of GABA<sub>A</sub> Receptor Subunits and Association with Patient Survival in Glioma |
| title_sort | gene expression of gaba sub a sub receptor subunits and association with patient survival in glioma |
| topic | GABA<sub>A</sub> receptor subunit gene GABA<sub>A</sub> receptor glioma glioblastoma brain tumor |
| url | https://www.mdpi.com/2076-3425/14/3/275 |
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