Dataset Information

DIA-Based Proteomic Analysis of Plasma Protein Profiles in Patients with Severe Acute Pancreatitis.

ABSTRACT: Acute pancreatitis (AP) is a pancreatic inflammatory disease that varies greatly in course and severity. To further the understanding of the pathology of AP, we carried out data-independent acquisition-based proteomic analyses using proteins extracted from the plasma of patients with severe acute pancreatitis (SAP) (experimental group) and healthy volunteers (control group). Compared to the control group, there were 35 differentially expressed proteins (DEPs) in the plasma of patients with SAP. Of those, the expression levels for 6 proteins were significantly increased, and 29 proteins were significantly decreased. Moreover, six candidate biomarkers-VWF, ORM2, CD5L, CAT, IGLV3-10, and LTF-were matched as candidate biomarkers of the disease severity of AP. The area under the receiver operating characteristic of 0.903 (95% CI: 0.839, 0.967) indicated that this combination of these six candidate biomarkers had a good prediction accuracy for predicting the severity of AP. Our study provides specific DEPs that may be useful in the diagnosis and prognosis of SAP, which suggests new theoretical bases for the occurrence and development of SAP and offers potential novel treatment strategies for SAP.

SUBMITTER: Li H

PROVIDER: S-EPMC9230633 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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DIA-Based Proteomic Analysis of Plasma Protein Profiles in Patients with Severe Acute Pancreatitis.

Li He H Xu Yansong Y Zhou Xin X Jin Taiyang T Wang Ziru Z Sun Yuansong Y Wang Haiping H Jiang Datong D Yin Chunlin C Shen Bing B Song Kai K

Molecules (Basel, Switzerland) 20220617 12

Acute pancreatitis (AP) is a pancreatic inflammatory disease that varies greatly in course and severity. To further the understanding of the pathology of AP, we carried out data-independent acquisition-based proteomic analyses using proteins extracted from the plasma of patients with severe acute pancreatitis (SAP) (experimental group) and healthy volunteers (control group). Compared to the control group, there were 35 differentially expressed proteins (DEPs) in the plasma of patients with SAP. ...[more]

PMID: 35745003

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Project description:Acute pancreatitis (AP) is a painful and potentially life-threatening disorder with the potential for therapeutic interventions. Biomarkers that characterize cases by severity and pathogenic mechanisms involved are not yet available but needed for the implementation of rational therapies. Here, we used shotgun proteomics to obtain information from plasma samples about local and systemic pathologies taking place during cases of alcoholic AP. Plasma was obtained at Kaunas University of Medicine Hospital (Lithuania) from 12 AP patients of alcohol related etiology (median age of 40) within 24 h of presentation, and 12 age-matched, healthy controls. Patients entered into the study had moderately severe AP with the following characteristics: mean blood lactate dehydrogenase level of 1127 mg/dl; median APACHEII score of 5.5 and mean IMRIE score of 3.5. 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-assisted sample preparation combined with tandem mass tag labeling for quantitation. Samples were analyzed using an Orbitrap Elite mass spectrometer for high resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our analysis revealed 31 proteins that exhibited significant 1.5-fold or higher increases in the AP compared to control patients, and six that were significantly decreased. Gene ontology analysis indicated a strong correlation with exosomal origin in the elevated proteins, with 29/31 (93.5%) 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. These results provide the methodology for proteomic analysis of plasma samples to discover novel biomarkers that characterize pancreatitis cases by pathogenic mechanism as well as disease activity at an early stage that is highly informative for routine clinical practice and clinical trials.

Project description:Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets' tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into the proteins that are involved in the platelets' activation response during ischemic stroke. It could be argued that this study lays the foundation for future mechanistic studies.

Dataset Information

DIA-Based Proteomic Analysis of Plasma Protein Profiles in Patients with Severe Acute Pancreatitis.

Publications

DIA-Based Proteomic Analysis of Plasma Protein Profiles in Patients with Severe Acute Pancreatitis.

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