Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development
Abstract
:1. Introduction
2. Results
2.1. Demographics, Chemical Exposure and Clinical Chemistries of Hemangiosarcoma and Control Cohorts
2.2. Metabolites Altered in the Development of vc-Mediated Hemangiosarcoma
2.3. Ontologies Implicated in the Development of VC-Mediated Hemangiosarcoma
2.4. Serum Inflammatory Proteins Bradykinin and C3 Are Elevated while Anti-Inflammatory Lipids Are Diminished in VC-Mediated Hemangiosarcoma
2.5. Serum Bile Acids Are Increased in VC-Mediated Hemangiosarcoma
2.6. Serum Gamma-Glutamyl Amino Acids Are Increased in VC-Mediated Hemangiosarcoma
2.7. Fibrin Degradation Products Are Elevated in VC-Mediated Hemangiosarcoma
2.8. Steroid Hormones, Steroid Hormone Metabolites and Gut-Derived Phenol Gastrodigenin Are Diminished in VC-Mediated Hemangiosarcoma
2.9. Random Forest Analysis Demonstrates That Metabolites from the Hemangiosarcoma and Control Are Statistically Distinct
3. Discussion
4. Materials and Methods
4.1. Subjects
4.2. Metabolomics
4.3. MetaCore Analysis
4.4. Random Forest Analysis
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Variable | Controls | Hemangiosarcoma |
---|---|---|
Number (unless otherwise noted) | 17 | 15 |
Age at sampling (years) | 50.5 ± 6.3 | 56.2 ± 10.9 |
BMI (kg/m2) | 27.1 ± 3.4 (n = 16) | 25.3 ± 2.1 (n = 12) |
Employment duration at sampling (years) | 25.5 ± 5.7 | 31.9 ± 12.0 |
Cumulative Exposure Rank Month (CERM) | 1156 ± 420.4 | 1266 ± 541.2 |
Duration of sample storage (years) | 35.0 ± 5.1 | 27.5 ± 12.0 a |
Analyte (Reference Range) | Controls | Hemangiosarcoma |
---|---|---|
Number (unless otherwise specified) | 17 | 12 |
Albumin (3.5–5.0 mg/dL) | 4.6 ± 0.2 | 4.4 ± 0.2 |
Total bilirubin (0.2–1.0 mg/dL) | 0.6 ± 0.2 | 0.6 ± 0.2 |
Alkaline phosphatase (38–126 U/L) | 70.5 ± 15.0 | 68.3 ± 36.2 |
AST (10–50 U/L) | 24.1 ± 15.6 | 27.8 ± 12.1 |
ALT (20–70 U/L) | 24.9 ± 18.4 | 19.8 ± 8.3 |
Triglycerides (10–190 mg/dL) | 153 ± 49.6 | 201 ± 101.6 (n = 8) |
Total cholesterol (120–200 mg/dL) | 213 ± 32.6 | 217 ± 32.5 (n = 8) |
Glucose (70–110 mg/dL) | 101 ± 17.3 | 105 ± 16.1 (n = 8) |
Ontology | p-Value | FDR |
---|---|---|
Bile acid biosynthesis | 3.45 × 10−7 | 1.17 × 10−5 |
Taurine and hypotaurine metabolism | 5.74 × 10−6 | 9.76 × 10−5 |
Cholesterol metabolism | 1.08 × 10−5 | 1.22 × 10−4 |
Cholesterol and bile acid homeostasis | 4.56 × 10−5 | 1.10 × 10−3 |
Renal secretion of inorganic electrolytes | 1.17 × 10−4 | 9.91 × 10−4 |
Renal secretion of organic electrolytes/rodent version | 2.57 × 10−4 | 1.75 × 10−3 |
Regulation of lipid metabolism_Regulation of acetyl-CoA carboxylase 1 activity | 3.88 × 10−4 | 2.20 × 10−3 |
Medium-chain saturated fatty acids synthesis | 5.72 × 10−4 | 2.78 × 10−3 |
Upregulation of IL-8 expression in colorectal cancer | 1.24 × 10−3 | 5.27 × 10−3 |
Carbohydrate metabolism_TCA and tricarboxylic acid transport | 1.97 × 10−3 | 4.74 × 10−2 |
Oxidative phosphorylation | 2.03 × 10−3 | 7.68 × 10−3 |
Metabolic diseases | 3.28 × 10−3 | 3.93 × 10−2 |
Oxidative stress Role of Sirtuin1 and PGC1-alpha in activation of antioxidant defense system | 4.31 × 10−3 | 1.46 × 10−2 |
Ontology | p-Value | FDR |
---|---|---|
Nicotine signaling in cholinergic neurons | 1.65 × 10−5 | 4.94 × 10−4 |
L-Lysine metabolism | 1.06 × 10−4 | 1.20 × 10−3 |
L-Tryptophan metabolism (part 2) | 1.20 × 10−4 | 1.20 × 10−3 |
Nicotine action | 1.48 × 10−4 | 5.02 × 10−3 |
(L)-carnitine pathway | 3.12 × 10−4 | 3.12 × 10−3 |
N-Acylethanolamines, HSRL5-transacylation pathway | 3.44 × 10−4 | 2.58 × 10−3 |
Development_Neuromuscular junction | 1.25 × 10−3 | 3.76 × 10−3 |
Neurophysiological process_Transmission of nerve impulse | 2.60 × 10−3 | 3.89 × 10−3 |
Renal secretion of organic electrolytes/Rodent version | 2.79 × 10−3 | 1.67 × 10−2 |
Cholesterol biosynthesis | 4.93 × 10−3 | 2.46 × 10−2 |
Steroid metabolism_Cholesterol biosynthesis | 9.27 × 10−3 | 4.64 × 10−2 |
Nicotine signaling in cholinergic neurons | 1.65 × 10−5 | 4.94 × 10−4 |
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Guardiola, J.J.; Hardesty, J.E.; Beier, J.I.; Prough, R.A.; McClain, C.J.; Cave, M.C. Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development. Int. J. Mol. Sci. 2021, 22, 5093. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105093
Guardiola JJ, Hardesty JE, Beier JI, Prough RA, McClain CJ, Cave MC. Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development. International Journal of Molecular Sciences. 2021; 22(10):5093. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105093
Chicago/Turabian StyleGuardiola, John J., Josiah E. Hardesty, Juliane I. Beier, Russell A. Prough, Craig J. McClain, and Matthew C. Cave. 2021. "Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development" International Journal of Molecular Sciences 22, no. 10: 5093. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105093