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Abstract: TH-PO1139

Quantitative Urine Proteomics by SWATH-MS Reflects Intricate Metabolic Processing in Cirrhosis Patients

Session Information

Category: Fluid, Electrolytes, and Acid-Base

  • 704 Fluid, Electrolyte, Acid-Base Disorders

Authors

  • Xu, Bo, Niigata University, Niigata, Japan
  • Hirao, Yoshitoshi, Niigata University, Niigata, Japan
  • Yamamoto, Keiko, Niigata University, Niigata, Japan
  • Narita, Ichiei, Niigata University, Niigata, Japan
  • Yamamoto, Tadashi, Niigata University, Niigata, Japan
Background

Cirrhosis of the liver often has no signs or symptoms until damages is extensive, 3-4 million people are suffered from cirrhosis in the world. However, early diagnosis and treatment are difficult due to cirrhosis could be leaded by a wide range of disease. The aim of this study is to reveal sophisticated metabolic processing pathway in cirrhosis patients by comparison of quantitative analysis of urine proteins between health volunteers and cirrhosis patients.

Methods

Urine proteins were purified by precipitation method from patients and health volunteers individually. After digestion, purified urine peptides were analyzed by optimized Sequential window acquisition of all theoretical mass spectra (SWATH-MS). ProteinPilot™ and PeakView™ were used for protein identification and SWATH data analysis respectively. Differentially expressed molecules were further analyzed by Gene Ontology (GO) and KEGG pathway analysis using DAVID.

Results

In total 2047 proteins were identified. 1425 proteins were reliably quantified in both groups. 861 proteins were observed with more than 2 times fold change (FC),415 proteins with over 5 times FC between cirrhosis and health control (HV) groups. We focused on these 415 molecules that were regulated in cirrhosis, since they will be supposed as potential molecules involved in the onset of cirrhosis. GO analysis indicated 282 of these 415 genes were clustered in extracellular exosome, and enrichment analysis revealed serine-type endopeptidase activity was the most significant over-represented molecular function for the 282 molecules. KEGG pathway analysis showed 38 proteins related to metabolic pathway. Glycolysis / Gluconeogenesis pathway is most significantly enriched. Low abundance proteins revealed that protein expression of cell adhesion, immune response, and proteolysis in cirrhosis patients.

Conclusion

Quantitative proteomic results of urine proteins from cirrhosis patients show significant increase of proteins related to the complement and coagulation cascades, regulation of actin cytoskeleton pathway, and decrease of proteins in the cell adhesion molecules (CAMs), endocytosis, PI3K/Akt signaling and phagosome pathways. Our pilot studies of cirrhosis patient urinary proteomes may promote to discover urine biomarkers of cirrhosis in the early stage of liver dysfunction.

Funding

  • Private Foundation Support