Phon Brandon Wee Siang, Bhuvanendran Saatheeyavaane, Ayub Qasim, Radhakrishnan Ammu Kutty, Kamarudin Muhamad Noor Alfarizal
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Malaysia.
School of Science, Monash University Malaysia, Bandar Sunway 47500, Malaysia.
Biology (Basel). 2023 Apr 25;12(5):648. doi: 10.3390/biology12050648.
A paradigm shift in preclinical evaluations of new anticancer GBM drugs should occur in favour of 3D cultures. This study leveraged the vast genomic data banks to investigate the suitability of 3D cultures as cell-based models for GBM. We hypothesised that correlating genes that are highly upregulated in 3D GBM models will have an impact in GBM patients, which will support 3D cultures as more reliable preclinical models for GBM. Using clinical samples of brain tissue from healthy individuals and GBM patients from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Chinese Glioma Genome Atlas (CGGA), and Genotype-Tissue Expression (GTEx) databases, several genes related to pathways such as epithelial-to-mesenchymal transition (EMT)-related genes (, , , , , ), angiogenesis/migration-related genes (, , , ), hypoxia-related genes (, ), stemness-related genes (, , , ), and genes involved in the Wnt signalling pathway (, ) were found to be upregulated in brain samples from GBM patients, and the expression of these genes were also enhanced in 3D GBM cells. Additionally, EMT-related genes were upregulated in GBM archetypes (wild-type ) that historically have poorer treatment responses, with said genes being significant predictors of poorer survival in the TCGA cohort. These findings reinforced the hypothesis that 3D GBM cultures can be used as reliable models to study increased epithelial-to-mesenchymal transitions in clinical GBM samples.
新的抗胶质母细胞瘤（GBM）抗癌药物临床前评估应发生范式转变，转向支持3D培养。本研究利用大量基因组数据库来研究3D培养作为GBM基于细胞模型的适用性。我们假设，在3D GBM模型中高度上调的相关基因将对GBM患者产生影响，这将支持3D培养作为更可靠的GBM临床前模型。使用来自健康个体的脑组织临床样本以及来自癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）、中国胶质瘤基因组图谱（CGGA）和基因型-组织表达（GTEx）数据库的GBM患者样本，发现与上皮-间质转化（EMT）相关基因（ 、 、 、 、 、 ）、血管生成/迁移相关基因（ 、 、 ）、缺氧相关基因（ ）、干性相关基因（ 、 、 ）以及参与Wnt信号通路的基因（ ）等通路相关的几个基因在GBM患者的脑样本中上调，并且这些基因在3D GBM细胞中的表达也增强。此外，EMT相关基因在历史上治疗反应较差的GBM原型（野生型 ）中上调，这些基因是TCGA队列中较差生存率的重要预测指标。这些发现强化了这样的假设，即3D GBM培养可作为可靠模型来研究临床GBM样本中上皮-间质转化增加的情况。
