Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development

• Published in: International journal of molecular sciences 2021-05, Vol.22 (10), p.5093
• Main Authors: Guardiola, John J, Hardesty, Josiah E, Beier, Juliane I, Prough, Russell A, McClain, Craig J, Cave, Matthew C
• Format: Article
• Language: English
• Subjects: Angiogenesis; angiosarcoma; Antiangiogenics; Bile; Bile acids; Biomarkers; Biomarkers - blood; Bradykinin; Case-Control Studies; Cholesterol; Cholinergics; Demography; Fibrin; Genotoxicity; Hemangiosarcoma - blood; Hemangiosarcoma - chemically induced; Hemangiosarcoma - diagnosis; Hemangiosarcoma - epidemiology; Humans; Inflammation; Latency; Lipids; Liver; Liver cancer; Liver Neoplasms - blood; Liver Neoplasms - chemically induced; Liver Neoplasms - diagnosis; Liver Neoplasms - epidemiology; Male; Mass spectroscopy; Metabolites; Metabolome; Metabolomics; Middle Aged; Occupational Diseases - blood; Occupational Diseases - chemically induced; Occupational Diseases - diagnosis; Occupational Diseases - epidemiology; Occupational exposure; Occupational Exposure - adverse effects; Ontology; Oxidative stress; Polyvinyl chloride; Polyvinyl Chloride - adverse effects; PVC; Taurine; United States - epidemiology; vinyl chloride
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22105093

High-level occupational vinyl chloride (VC) exposures have been associated with hepatic hemangiosarcoma, which typically develops following a long latency period. Although VC is genotoxic, a more comprehensive mode of action has not been determined and diagnostic biomarkers have not been established. The purpose of this study is to address these knowledge gaps through plasma metabolomics. Plasma samples from polyvinyl chloride polymerization workers who developed hemangiosarcoma (cases, = 15) and VC exposure-matched controls ( = 17) underwent metabolomic analysis. Random forest and bioinformatic analyses were performed. Cases and controls had similar demographics and routine liver biochemistries. Mass spectroscopy identified 606 known metabolites. Random forest analysis had an 82% predictive accuracy for group classification. 60 metabolites were significantly increased and 44 were decreased vs. controls. Taurocholate, bradykinin and fibrin degradation product 2 were up-regulated by greater than 80-fold. The naturally occurring anti-angiogenic phenol, 4-hydroxybenzyl alcohol, was down-regulated 5-fold. Top affected ontologies involved: (i) metabolism of bile acids, taurine, cholesterol, fatty acids and amino acids; (ii) inflammation and oxidative stress; and (iii) nicotinic cholinergic signaling. The plasma metabolome was differentially regulated in polyvinyl chloride workers who developed hepatic hemangiosarcoma. Ontologies potentially involved in hemangiosarcoma pathogenesis and candidate biomarkers were identified.