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PROTEOMIC IDENTIFICATION OF NOVEL BIOMARKERS OF ETHANOL ACUTE PANCREATITIS
Aiste Gulla*1,2, Richard Waldron3, Aurelia Lugea3, Stephen J. Pandol3
1Department of Surgery, Georgetown University Hospital, Great Falls, VA; 2Department of Surgery, Vilnius University, Vilnius, Lithuania; 3Department of Medicine, Cedars-Sinai Medical Center and University of California, Los Angeles, CA
Introduction: Acute pancreatitis (AP) is a painful and potentially life-threatening disorder with no effective therapeutic remedies. The severity of the disease varies widely and only limited biomarkers and severity scores are available to assess its severity. Therefore, an urgent need is to develop additional biomarkers that can improve clinical course and minimize mortality in AP.
Methods: Patient serum was obtained from 12 male AP patients of alcohol related etiology (median age of 40) within 24 h of presentation, and 12 controls. Severity in AP patients was as a correlate of tissue damage was estimated by blood lactate dehydrogenase, with an average value of 1127 mg/dl. Median APACHEII score was 5.5, and IMRIE score was 3.5, indicating moderate to severe AP (please see the accompanying table for details). For proteomic analysis, less abundant proteins in plasma samples were enriched using Top 12 abundant protein depletion columns. Further processing was performed by a modified filter-associated sample preparation combined with tandem mass tag labeling for quantitation. Samples were analyzed by Orbitrap Elite instrument for state-of-the-art high resolution liquid chromatography-tandem mass spectrometry.
Results: Our analysis revealed that 44 proteins exhibited 1.5-fold or higher increase in the AP compared to control patients. Gene ontology analysis indicated a strong correlation with exosomal origin in the elevated proteins, with 35/44 (80%) associated with this extracellularly-secreted compartment. Elevated proteins included established and proposed biomarkers of AP including C-reactive protein, LPS-binding protein, intercellular adhesion molecule-1, and von Willebrand factor, as well as several novel potential biomarkers.
Conclusions: These results suggest that we are discovering novel biomarkers which can be used for measuring the severity of pancreatitis at any point in time during the course of disease.
Table for Serum Biomarker Proteonomic Study_AGA 2017
| Age | LDH | APACHE II | IMRIE | MODS | | | 34 | 420 | 1 | 1 | 4 | | | 25 | 447 | 0 | 1 | 0 | | | 40 | 539 | 2 | 1 | 2 | | | 45 | 644 | 7 | 5 | 2 | | | 49 | 848 | 7 | 4 | 3 | | | 33 | 961 | 4 | 3 | 1 | | | 41 | 1194 | 11 | 6 | 3 | | | 44 | 1280 | 8 | 5 | 6 | | | 66 | 1384 | 11 | 4 | 5 | | | 32 | 1508 | 1 | 3 | 3 | | | 38 | 1818 | 3 | 3 | 1 | | | 36 | 3028 | 10 | 6 | 10 | | | 39.0 | 1077.5 | 5.5 | 3.5 | 3.0 | Median | | 40.3 | 1172.6 | 5.4 | 3.5 | 3.3 | Average | | 10.4 | 735.6 | 4.1 | 1.8 | 2.7 | STDEV | | | | | | | |
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