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Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression

ABSTRACT: Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among the patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care, reduce morbidity and mortality. This is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery Top-down Proteomics (TDP) to detect differentially expressed proteoforms (DEPs) in the plasma of patients with cirrhosis with the goal to identify candidate biomarkers of disease progression. 663 DEPs were identified across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the progressive stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in numerous metabolic, oxidative, immunological, and hematological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Human

SUBMITTER: Neil Kelleher

PROVIDER: MSV000094311 | MassIVE | Wed Mar 13 08:41:00 GMT 2024

REPOSITORIES: MassIVE

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Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression

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