Proteomic Signature of Acute Liver Failure: From Discovery and Verification in a Pig Model to Confirmation in Humans.
Mol Cell Proteomics
; 16(7): 1188-1199, 2017 07.
Article
in En
| MEDLINE
| ID: mdl-28336726
ABSTRACT
Acute liver failure (ALF) is a fatal condition hallmarked by rapid development. The present study aimed to describe the dynamic alterations of serum proteins associated with ALF development, and to seek for novel biomarkers of ALF. Miniature pigs (n = 38) were employed to establish ALF models by infusing d-galactosamine (GALN, 1.3 g/kg). A total of 1310 serum proteins were compared in pooled serum samples (n = 10) before and 36 h after GALN administration through label-free quantitation (LFQ) based shotgun proteomics. Functional analysis suggested a significant enrichment of ALF-related proteins involved in energy metabolism. Temporal changes of 20 energy metabolism related proteins were investigated in individual pigs (n = 8) via parallel reaction monitoring (PRM) based targeted proteomics. In addition, mitochondrion degeneration and gene expression alteration of aerobic metabolism genes were confirmed in GALN-insulted pig liver. In clinical validation study enrolled 34 ALF patients and 40 healthy controls, fructose-1,6-bisphosphatase 1 (FBP1) showed a prognostic value for short-term survival (30 days) equal to that of the Model of End-stage Liver Disease score (ROC-AUC = 0.778). Survival analysis suggested significantly higher death-related hazard in ALF patients with higher FBP1 levels (>16.89 µg/dL) than in those with lower FBP1 levels (p = 0.002). Additionally, serum retinol binding protein 4 (RBP4) level was found decreased prior to ALT elevation in GALN-insulted pig model. We also confirmed that serum level of RBP4 is significantly lower in ALF patients (p < 0.001) as compared with healthy controls. In summary, this translational study, displayed by multistaged proteomics techniques, unveiled underlying functional changes related to the development of ALF and facilitated the discovery of novel ALF markers.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Liver Failure, Acute
/
DNA Helicases
/
Proteomics
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DNA-Binding Proteins
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Retinol-Binding Proteins, Plasma
Type of study:
Prognostic_studies
Limits:
Adult
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Animals
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Mol Cell Proteomics
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2017
Document type:
Article