Integrated Multi‐Omics Analysis of Human Cerebrospinal Fluid in Traumatic Spinal Cord Injury: An Exploratory Pilot Study

OBJECTIVE: Acute traumatic spinal cord injury (TSCI) is a devastating neurological disorder with limited therapeutic options. We aimed to characterize the human cerebrospinal fluid (CSF) microenvironment to identify novel multi-omics signatures and potential mechanistic hypotheses. METHODS: CSF from 13 acute cervical TSCI patients and 13 controls was prospectively collected. A discovery cohort (n = 10) underwent untargeted proteomics and metabolomics. Following differential and functional enrichment analyses, sequential multi-omics integration was applied to extract cross-omics features. Prioritized candidates were subsequently validated via ELISA and targeted metabolomics in an independent validation cohort (n = 16). RESULTS: We identified 216 differentially expressed proteins and 26 metabolites, highlighting extensive extracellular matrix remodeling alongside profound purine and amino acid metabolism dysregulation. Integrated analyses converged on downregulated mitochondrial aspartate aminotransferase (GOT2) as a candidate marker. Targeted correlation analysis revealed that GOT2 selectively associated with specific co-mapped metabolites that were concurrently downregulated, notably methionine and 4-acetamidobutanoic acid. The GOT2-associated metabolic signature was experimentally validated in the independent cohort. CONCLUSIONS: This exploratory multi-omics study unveils the acute human TSCI molecular landscape, nominating a novel GOT2-associated metabolic signature that warrants further mechanistic investigation regarding its pathogenic implications and potential therapeutic relevance.