Altered plasma metabolite levels can be detected years before a glioma diagnosis

• Published in: JCI Insight
• Main Authors: Löding, S, Andersson, U, Kaaks, R, Schulze, MB, Pala, V, Urbarova, I, Amiano, P, Colorado-Yohar, SM, Guevara, M, Heath, AK, Chatziioannou, AC, Johansson, M, Nyberg, L, Antti, H, Björkblom, B, Melin, B
• Format: Article in Journal/Newspaper
• Language: English
• Published: American Society for Clinical investigation 2023
• Subjects: Northern Sweden
• Online Access: http://hdl.handle.net/10044/1/106286; https://doi.org/10.1172/jci.insight.171225

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.