Bioinformatics analysis of the spinal cord injured plasma proteome: A focus on the liver

Godwin, Morgan, Brown, Sharon J., Bernardo-Harrington, Gabriel Mateus ORCID: https://orcid.org/0000-0001-6075-3619, Budithi, Srinivasa C., Riddell, John S., Hulme, Charlotte H. and Wright, Karina T. 2026. Bioinformatics analysis of the spinal cord injured plasma proteome: A focus on the liver. Livers 6 (3) , p. 38. 10.3390/livers6030038

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Abstract

Background: Emerging evidence indicates that the liver plays a key role in spinal cord injury (SCI) pathophysiology. Method: This study reanalysed published proteomic datasets from rat models and patients with SCI using bioinformatics and literature/database searches. The aim was to identify liver-specific molecular signatures in SCI blood samples and to link these to severity and neurological recovery at various time points (acute/sub-acute and chronic). Results: Across species, a high proportion of injury severity and neurological recovery-associated proteins were linked to liver function. Notably, non-improvers exhibited prolonged sub-acute proinflammatory responses. These changes were not restricted to classical acute-phase reactants but reflected coordinated alterations in hepatic metabolic and synthetic pathways. Pathway analysis consistently highlighted Liver X Receptor /Retinoic X Receptor (LXR/RXR), complement system/cascade and DHCR24 signalling pathways, with predicted directional changes linked to recovery status. Several proteins were identified and categorised as markers of liver dysfunction, metabolic function, complement/coagulation factors and/or acute-phase proteins. Alpha-2-HS-glycoprotein (AHSG) and afamin (AFM) were commonly dysregulated across species datasets, suggesting conserved roles in inflammation and lipid metabolism. Further associations with liver pathologies such as fibrosis and cirrhosis, particularly in non-improvers, were identified. Conclusion This work builds on emerging evidence of hepatic involvement in SCI by providing cross-species, time-resolved proteomic support for altered liver-associated protein output following injury. Together, these findings underscore the central role of hepatic responses in SCI, highlighting liver-associated proteins and pathways as candidate biomarkers that may aid in stratifying recovery trajectories and informing clinical prognostication. Keywords: spinal cord injury (SCI); liver dysfunction; proteomics; bioinformatics

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	MDPI
ISSN:	2673-4389
Date of First Compliant Deposit:	28 July 2026
Date of Acceptance:	23 April 2026
Last Modified:	28 Jul 2026 10:45
URI:	https://orca.cardiff.ac.uk/id/eprint/188528

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