Biomarker Discovery in Liver Disease Using Untargeted Metabolomics in Plasma and Saliva

• Published in: International journal of molecular sciences Vol. 25; no. 18; p. 10144
• Main Authors: Daniels, Noah J, Hershberger, Courtney E, Kerosky, Matthew, Wehrle, Chase J, Raj, Roma, Aykun, Nihal, Allende, Daniela S, Aucejo, Federico N, Rotroff, Daniel M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-09-2024; MDPI
• Subjects: Adult; Aged; Biological markers; biomarker discovery; Biomarkers; Biomarkers - blood; Blood plasma; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - metabolism; Development and progression; Diabetes; Diagnosis; Etiology; Female; Health aspects; hepatocellular carcinoma; Humans; Identification and classification; Liver cancer; Liver cirrhosis; Liver Cirrhosis - blood; Liver Cirrhosis - diagnosis; Liver Cirrhosis - metabolism; liver disease; Liver diseases; Liver Diseases - blood; Liver Diseases - metabolism; Liver Neoplasms - blood; Liver Neoplasms - metabolism; Male; Medical prognosis; Metabolism; Metabolites; Metabolome; Metabolomics; Metabolomics - methods; Middle Aged; NAFLD; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - metabolism; Obesity; Physiological aspects; Plasma; Regression analysis; Saliva; Saliva - metabolism; Salivary glands; secretions; Weight control; United States; NAFLD; liver disease; metabolomics; biomarker discovery; hepatocellular carcinoma; liver cirrhosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251810144

Chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC), continue to be a global health burden with a rise in incidence and mortality, necessitating a need for the discovery of novel biomarkers for HCC detection. This study aimed to identify novel non-invasive biomarkers for these different liver disease states. We performed untargeted metabolomics in plasma (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 34) and saliva samples (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 22) to test for significant metabolite associations with each disease state. Additionally, we identified enriched biochemical pathways and analyzed correlations of metabolites between, and within, the two biofluids. We identified two salivary metabolites and 28 plasma metabolites significantly associated with at least one liver disease state. No metabolites were significantly correlated between biofluids, but we did identify numerous metabolites correlated within saliva and plasma, respectively. Pathway analysis revealed significant pathways enriched within plasma metabolites for several disease states. Our work provides a detailed analysis of the altered metabolome at various stages of liver disease while providing some context to altered pathways and relationships between metabolites.