Spinelli Sonia, Garbarino Andrea, Pavanello Marco, Candiano Giovanni, Panfoli Isabella, Bruschi Maurizio
Laboratory of Molecular Nephrology, Istituto Giannina Gaslini IRCCS, Genoa, Italy.
Department of Neurosurgery, Istituto Giannina Gaslini IRCCS, Genoa, Italy.
Expert Rev Proteomics. 2025 Jun;22(6):217-224. doi: 10.1080/14789450.2025.2514841. Epub 2025 Jun 4.
Brain solid tumors are a leading cause of cancer-related mortality at all ages. The updated 2021WHO Central Nervous System tumor classification is based on genomic diagnostics. Nonetheless, extracellular vesicles (EVs) proteomics is a platform for protein biomarker discovery in brain tumor patient management. Tumor metabolic reprogramming, also through epigenetic mechanisms, is central to cancer. EVs transfer proteins and nucleic acids that relay the metabolic and redox state of the parent cells.
This review addresses the biomarker discovery and translation focusing on recent (from 2022 to 2024 PubMed) proteomic studies of EVs in brain tumor patients, selected for their focus on metabolic aspects. The most treatable adult brain tumor is isocitrate dehydrogenase-mutated glioma. Minimally invasive collection of EVs from cerebrospinal fluid or prospectively blood allows proteomic and metabolic analysis of the parent tumor cells.
The CSF EVs express key CNS tumor biomarkers and therapy targets undetectable in whole CSF and relay the brain tumor metabolic adaptations. Metabolic dependencies can represent potential therapy targets. The clinical implications of biomarker EV proteomic discovery represent a promising platform for diagnostic and prognostic purposes in brain solid tumors, a leading cause of cancer-related mortality at all ages.
脑实体瘤是各年龄段癌症相关死亡的主要原因。2021年更新的世界卫生组织中枢神经系统肿瘤分类基于基因组诊断。尽管如此，细胞外囊泡（EVs）蛋白质组学是在脑肿瘤患者管理中发现蛋白质生物标志物的一个平台。肿瘤代谢重编程，同样也通过表观遗传机制，是癌症的核心。细胞外囊泡转运蛋白质和核酸，这些物质传递母细胞的代谢和氧化还原状态。
本综述探讨生物标志物的发现与转化，重点关注近期（2022年至2024年PubMed）针对脑肿瘤患者细胞外囊泡的蛋白质组学研究，这些研究因其对代谢方面的关注而被选中。最易治疗的成人脑肿瘤是异柠檬酸脱氢酶突变型胶质瘤。从脑脊液或前瞻性采集的血液中微创收集细胞外囊泡，可对母肿瘤细胞进行蛋白质组学和代谢分析。
脑脊液细胞外囊泡表达关键的中枢神经系统肿瘤生物标志物和在全脑脊液中无法检测到的治疗靶点，并传递脑肿瘤的代谢适应性。代谢依赖性可能代表潜在的治疗靶点。生物标志物细胞外囊泡蛋白质组学发现的临床意义，是脑实体瘤诊断和预后的一个有前景的平台，脑实体瘤是各年龄段癌症相关死亡的主要原因。
