Monteiro Jander M, Dalmolin Matheus, Fernandes Marcelo A C, Ramos Jaqueline I R, Ribas Carmen A P M, Tabushi Fernando I, Roesler Rafael, Isolan Gustavo R
Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba 80730-000, Brazil.
InovAI Lab, nPITI/IMD, Federal University of Rio Grande do Norte, Natal 59078-970, Brazil.
Brain Sci. 2024 Nov 15;14(11):1146. doi: 10.3390/brainsci14111146.
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.
大脑中大多数快速抑制性神经传递是通过激活γ-氨基丁酸（GABA）A型（GABA A）受体介导的，该受体是一种配体门控离子通道。通过GABA结合激活GABA受体可使Cl离子内流进入细胞内，从而诱导细胞超极化。每个GABA受体由五个亚基组合而成，并且有几个亚基已被提出作为癌症的生物标志物和治疗靶点。在这里，我们展示了编码GABA受体β亚基（即β1、β2和β3）的基因在髓母细胞瘤（MB，最常见的儿童恶性脑肿瘤）的四个不同分子亚组中的表达情况。我们还展示了GABA受体β亚基与MB患者总生存期（OS）的关联。使用先前描述的包含763个MB肿瘤样本的数据集分析了编码GABA受体β亚基的基因表达情况。将患者分为高基因表达组和低基因表达组，并使用Kaplan-Meier估计法来检验基因表达水平与患者OS之间的关系。在四个分子亚组中的每一个亚组内，β1高表达都与更好的OS相关。与所有其他亚组相比，β2基因在3型MB中显示出更高的转录水平，并且β2高表达与3型肿瘤的更好预后相关。β3表达在3型和4型MB中显著更高，并且β3基因的高表达与音猬因子（SHH）亚组中更长的OS相关。β1、β2和β3的高表达以亚组特异性方式与患者更长的OS相关。这些结果表明含β亚基的GABA受体在影响MB进展中发挥作用。
