在胶质母细胞瘤诊断之前数年，组织和血液的遗传和代谢变化被报道发生。由于目前胶质母细胞瘤的检测较晚，早期液体活检可能会影响患者的生活质量和预后。在这里，我们展示了一项嵌套式病例对照研究，包括了来自北瑞典健康与疾病研究（NSHDS）和欧洲癌症与营养前瞻性研究（EPIC）的550例胶质母细胞瘤前诊断病例和550例健康对照。我们发现了93个与胶质母细胞瘤发展相关并在诊断前长达8年的显著改变的代谢物。从这些代谢物中，有一个由20个精选代谢物组成的面板在NSHDS和EPIC群体中显示了与疾病的强相关性和一致的发展模式，并且独立于生物性别有利地区分了未来的病例和对照。血液代谢物面板还成功地在NSHDS中将低级别胶质母细胞瘤和胶质母细胞瘤病例与对照区分开来，在诊断前8年（胶质母细胞瘤AUC=0.85，P=3.1e-12；胶质母细胞瘤AUC=0.85，P=6.3e-8），以及在EPIC中，在诊断前2年（胶质母细胞瘤AUC=0.81，P=0.005；胶质母细胞瘤AUC=0.89，P=0.04）。通路富集分析检测到与TCA循环、Warburg效应、糖异生、半胱氨酸、丙酮酸和酪氨酸代谢相关的代谢物受到最大影响。

Genetic and metabolic changes in tissue and blood are reported to occur several years before glioma diagnosis. As gliomas are currently detected late, a liquid biopsy for early detection could impact the quality of life and prognosis of patients. Here, we present a nested case-control study of 550 pre-diagnostic glioma cases and 550 healthy controls, from the Northern Sweden Health and Disease study (NSHDS) and the European Prospective Investigation into Cancer and Nutrition (EPIC) study. We identified 93 significantly altered metabolites related to glioma development up to eight years before diagnosis. Out of these metabolites, a panel of 20 selected metabolites showed strong disease correlation and consistent progression pattern towards diagnosis in both the NSHDS and EPIC cohorts, and separated favorably future cases from controls independently of biological sex. The blood metabolite panel also successfully separated both lower grade glioma and glioblastoma cases from controls, up to eight years before diagnosis in NSHDS (glioma AUC=0.85, P=3.1e-12; glioblastoma AUC=0.85, P=6.3e-8), and up to two years before diagnosis in EPIC (glioma AUC=0.81, P=0.005; glioblastoma AUC=0.89, P=0.04). Pathway enrichment analysis detected metabolites related to the TCA-cycle, Warburg effect, gluconeogenesis, cysteine-, pyruvate- and tyrosine metabolism as the most affected.