多形性胶质母细胞瘤 (GBM) 是成年人中最常见、最具侵袭性的脑肿瘤，预后较差，平均生存期为 14-15 个月。为了全面了解蛋白质组并确定新的治疗靶点，本研究主要集中于 RasV12 诱导的 GBM 的差异丰度蛋白（DAP）。 RasV12 是一种组成型活性 Ras 突变体，通过持续激活信号通路导致肿瘤生长失控，对肿瘤进展至关重要。本研究使用了 RasV12 过表达的转基因果蝇模型，并使用 repo-GAL4 驱动系（特别是在神经胶质细胞中）来研究 GBM。基于高分辨率质谱 (HRMS) 的 GBM 幼虫中枢神经系统蛋白质组学分析鉴定出三种针对线粒体的新型 DAP。通过 HRMS 鉴定的这些 DAP，可能是马来酰乙酰乙酸异构酶 2 (Q9VHD2)、双功能亚甲基四氢叶酸脱氢酶 (Q04448) 和谷氨酰胺合成酶 1 (P20477)，并通过 qRT-PCR 进一步验证。蛋白质-蛋白质相互作用分析揭示了 RasV12 和 DAP 之间的相互作用，以及与 Drp1、Marf、Parkin 和 HtrA2 等线粒体动力学调节因子的功能联系。值得注意的是，在 GBM 进展过程中观察到 Q9VHD2、P20477 和 Q04448 表达的改变，这为线粒体动态调节因子参与 RasV12 诱导的 GBM 病理生理学提供了新的见解。

Glioblastoma multiforme (GBM) is the most prevalent and aggressive brain tumor found in adult humans with a poor prognosis and average survival of 14-15 months. In order to have a comprehensive understanding of proteome and identify novel therapeutic targets, this study focused mainly on the differentially abundant proteins (DAPs) of RasV12-induced GBM. RasV12 is a constitutively active Ras mutant form essential for tumor progression by continuously activating signaling pathways leading to uncontrolled tumor growth. This study used a transgenic Drosophila model with RasV12 overexpression using the repo-GAL4 driver line, specifically in glial cells, to study GBM. The high-resolution mass spectrometry (HRMS)-based proteomic analysis of the GBM larval central nervous system identified three novel DAPs specific to mitochondria. These DAPs, probable maleylacetoacetate isomerase 2 (Q9VHD2), bifunctional methylene tetrahydrofolate dehydrogenase (Q04448), and glutamine synthetase1 (P20477), identified through HRMS were further validated by qRT-PCR. The protein-protein interaction analysis revealed interactions between RasV12 and DAPs, with functional links to mitochondrial dynamics regulators such as Drp1, Marf, Parkin, and HtrA2. Notably, altered expressions of Q9VHD2, P20477, and Q04448 were observed during GBM progression, which offers new insights into the involvement of mitochondrial dynamic regulators in RasV12-induced GBM pathophysiology.