The First School of Clinical Medicine, Southern Medical University, Guangzhou, P.R. China.
Department of Neurosurgery, The General Hospital of Chinese PLA Central Theater Command, Wuhan, P.R. China.
Cancer Genomics Proteomics. 2024 Mar-Apr;21(2):186-202. doi: 10.21873/cgp.20440.
BACKGROUND/AIM: Gliomas are the most prevalent brain tumors with metabolic alterations playing a pivotal role in disease progression. However, the precise coordination of metabolic alterations with tumor-promoting cellular mechanisms, leading to tumor initiation, progression, and aggressiveness, resulting in poor outcomes, remains poorly understood in gliomas.
We conducted a metabolism-targeted differential gene expression analysis using glioma patients' expression profiling data from The Cancer Genome Atlas (TCGA) database. In addition, pathway enrichment analysis, gene set enrichment analysis (GSEA), transcription factor prediction, network construction, and correlation analyses were performed. Survival analyses were performed in R. All results were validated using independent GEO expression datasets.
Metabolism-targeted analysis identified 5 hits involved in diverse metabolic processes linking them to disease aggressiveness in gliomas. Subsequently, we established that cell cycle progression and hyper-proliferation are key drivers of tumor progression and aggressiveness in gliomas. One of the identified metabolic hits, DNA primase 2 (PRIM2), a gene involved in DNA replication was found directly associated with cell cycle progression in gliomas. Furthermore, our analysis indicated that PRIM2, along with other cell cycle-related genes, is under the control of and regulated by the oncogenic MYC transcription factor in gliomas. In addition, PRIM2 expression alone is enough to predict MYC-driven cell cycle progression and is associated with tumor progression, aggressive disease state, and poor survival in glioma patients.
Our findings highlight PRIM2 as a marker of MYC-driven cell cycle progression and hyper-proliferation, disease onset and progression, tumor aggressiveness, and poor survival in glioma patients.
背景/目的：神经胶质瘤是最常见的脑肿瘤，其代谢改变在疾病进展中起着关键作用。然而，代谢改变与促进肿瘤发生、发展和侵袭的细胞机制之间的确切协调，导致肿瘤的起始、进展和侵袭性，导致不良预后，在神经胶质瘤中仍知之甚少。
我们使用来自癌症基因组图谱（TCGA）数据库的神经胶质瘤患者表达谱数据进行了代谢靶向差异基因表达分析。此外，还进行了通路富集分析、基因集富集分析（GSEA）、转录因子预测、网络构建和相关性分析。在 R 中进行了生存分析。所有结果均使用独立的 GEO 表达数据集进行验证。
代谢靶向分析确定了 5 个涉及多种代谢过程的命中，将它们与神经胶质瘤的疾病侵袭性联系起来。随后，我们建立了细胞周期进展和过度增殖是神经胶质瘤肿瘤进展和侵袭性的关键驱动因素。鉴定出的代谢命中之一，参与 DNA 复制的 DNA 引物 2（PRIM2）基因，与神经胶质瘤中的细胞周期进展直接相关。此外，我们的分析表明，PRIM2 与其他细胞周期相关基因一起，受神经胶质瘤中致癌 MYC 转录因子的控制和调节。此外，PRIM2 表达本身足以预测 MYC 驱动的细胞周期进展，并与神经胶质瘤患者的肿瘤进展、侵袭性疾病状态和不良生存相关。
我们的研究结果强调 PRIM2 是 MYC 驱动的细胞周期进展和过度增殖、疾病起始和进展、肿瘤侵袭性和不良生存的标志物。
