ArticleResearch square2026
Temporal Integration of Serum Proteomics, Metabolomics and MRI Tumor Volumetrics via Deep Learning Identifies Systemic Mediators of Glioblastoma Response to Chemoradiotherapy.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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15 authors.
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Abstract
Background: Glioblastomas (GBM) are highly aggressive, treatment-resistant brain tumors lacking clinically actionable, noninvasive prognostic biomarkers. Tumor response after standard-of-care chemoradiation (CRT) is difficult to interpret on imaging, and post-CRT MRI changes have not been well linked to molecular features or potential biomarkers. Purpose: We evaluated differential proteomic and metabolomic expression in patient serum in relation to AI-segmented MRI volume changes after CRT to integrate clinical, molecular, and imaging data with patient outcomes. Materials and Methods: Fifty- five clinically annotated GBM patients provided serum samples pre- and post-CRT, analyzed using the SomaScan Results: AI-derived CE volumes decreased significantly during the early period, while edema increased significantly during the late period. CE changes were associated with metabolic pathways relevant to GBM biology, including epithelial-mesenchymal transition, in ammatory response, coagulation, and interferon-γ signaling. Clustering revealed two groups with distinct survival outcomes; CE alterations were significantly greater in the low-survival cluster (p = 0.02). Multiomic analysis (MOGSA) showed downregulation of key metabolic pathways in the low-survival group, including the citric acid cycle, Warburg effect, amino acid metabolism, oncogenic 2-hydroxyglutarate activity, and purine metabolism. Contributing metabolites included fumarate, succinate, citrate, and 2-hydroxyglutarate, while major proteomic contributors included MPC1, PDHB, DLAT, DLST, IDH3, SDHB, and FH. Conclusions: AI-derived MRI tumor-volume changes after CRT correspond to specific serum proteomic and metabolomic alterations, highlighting metabolic pathways linked to contrast-enhancing tissue dynamics in GBM.
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