Serum SOS1 as a prognostic biomarker and therapeutic target for progressive liver disease

  • iScience. 2026 Jun 17;29(7):116430. doi: 10.1016/j.isci.2026.116430.
Peter U Amadi  1  2 ,  Govind S Gill  1 ,  Chiamaka W Amadi  2 ,  Justice O Osuoha  3 ,  Prince C Odika  4 ,  Raj M Patel  5 ,  Suha J Jarad  5 ,  Hong-Mei Gu  1 ,  Moattar Latif  1 ,  Joy A Amadi  6 ,  Celestine N Ekweogu  7 ,  Melford U Elendu  7 ,  Emmanuel N Agomuo  2 ,  Alastair O'Brien  8 ,  Barbora de Courten  9 ,  Ralf Weiskirchen  10 ,  Da-Wei Zhang  1
Affiliations
  • 1. Department of Pediatrics, Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB, Canada.
  • 2. Department of Biochemistry, Imo State University, Owerri, Nigeria.
  • 3. School of Chemistry, Monash University, Melbourne, VIC, Australia.
  • 4. Department of Biology, St. Mary's University, Halifax, NS, Canada.
  • 5. Department of Biochemistry, Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB, Canada.
  • 6. Department of Human Nutrition and Dietetics, Imo State University, Owerri, Nigeria.
  • 7. Department of Medical Biochemistry, Imo State University, Owerri, Nigeria.
  • 8. Institute for Liver and Digestive Health, University College London, London, UK.
  • 9. School of Health and Biomedical Sciences, RMIT University, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia.
  • 10. Institute of Molecular Pathobiochemistry, Experimental Gene Therapy, and Clinical Chemistry (IFMPEGKC) at RWTH University Aachen, Aachen, Germany.
PMID: 42369045 DOI: 10.1016/j.isci.2026.116430
Abstract

Given the lack of a reliable prognostic biomarker for the serial progression of chronic liver disease, we investigated SOS1 linked to stellate cells-driven liver disease progression. A cohort of 556 participants stratified into F0-F1, F2-F3, F4, and HCC, was followed for up to 36 months, measuring serial SOS1 and comparators, modeling outcome discrimination and trajectories, and validating biologic relevance via SOS1 inhibition in stellate cells and a chronic-injury mouse model. SOS1 increased stepwise with disease stage and correlated with APRI and FIB-4 (p < 0.001). Higher baseline SOS1 predicted mortality (HR 1.78, 95% CI 1.32-2.41), outperforming AFP and MELD, with AUC(t) = 0.82 at 36 months. Steeper SOS1 trajectories conferred higher death risk. In TCGA-LIHC, SOS1 remained independently prognostic. Pharmacological inhibition of SOS1 reduced fibrogenic gene expression and attenuated fibrosis in vivo and in vitro. SOS1 showed a stage-responsive, quantitatively validated biomarker linking clinical risk stratification with fibrogenic biology in liver disease.

Keywords
health sciences.
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