Quantitative metabolic analysis of plasma extracellular vesicles for the diagnosis of severe acute pancreatitis

Abstract

Background Severe acute pancreatitis (SAP) is the most common gastrointestinal disease and is associated with unpredictable seizures and high mortality rates. Despite improvements in the treatment of acute pancreatitis, the timely and accurate diagnosis of SAP remains highly challenging. Previous research has shown that extracellular vesicles (EVs) in the plasma have significant potential for the diagnosis of SAP since the pancreas can release EVs that carry pathological information into the peripheral blood in the very early stages of the disease. However, we know very little about the metabolites of EVs that might play a role in the diagnosis of SAP. Methods Here, we performed quantitative metabolomic analyses to investigate the metabolite profiles of EVs isolated from SAP plasma. We also determined the metabolic differences of EVs when compared between healthy controls, patients with SAP, and those with mild acute pancreatitis (MAP). Results A total of 313 metabolites were detected, mainly including organic acids, amino acids, fatty acids, and bile acids. The results showed that the metabolic composition of EVs derived from SAP and MAP was significantly different from those derived from healthy controls and identified specific differences between EVs derived from patients with SAP and MAP. On this basis, we identified four biomarkers from plasma EVs for SAP detection, including eicosatrienoic acid (C20:3), thiamine triphosphate, 2-Acetylfuran, and cis-Citral. The area under the curve (AUC) was greater than 0.95 for both discovery (n = 30) and validation (n = 70) sets. Conclusions Our data indicate that metabolic profiling analysis of plasma EVs and the screening of potential biomarkers are of significant potential for improving the early diagnosis and severity differentiation of acute pancreatitis. Graphical abstract

Multi-Omics Integrative Approach of Extracellular Vesicles: A Future Challenging Milestone

“…For example, Clos-Garcia et al reported an elevated level of the steroid hormone dehydroepiandrosterone sulphate (DHEAS) in urinary EVs from prostate cancer patients [ 92 ]. In addition, recently Lou et al identified four metabolites as potential markers for severe acute pancreatitis (SAP) diagnosis, including eicosatrienoic acid (C20:3), thiamine triphosphate, 2-Acetylfuran, and cis-Citral [ 93 ]. Beyond clinical applications, EVs metabolome might also provide alternative information on EVs as metabolically active machines.…”

“…The other encouraging application of lipidomics is the research of EVs lipid biomarkers. For example, Zhao et al investigated plasma derived-EVs lipidomes of women in the early second trimester with preterm and fully-term births [ 101 ], while Luo et al focused on the identification of potential metabolites biomarkers in pleural effusion-derived EVs for the rapid and correct diagnosis of tuberculosis pleural effusion (TPE) and malignancy pleural effusion (MPE) through both a metabolomic and lipidomic approach [ 93 ]. Nowadays, EVs represent wonderful candidates for novel ground-breaking drug delivery systems and for this reason, EVs lipidomics deals with an important challenge.…”

Multi-Omics Integrative Approach of Extracellular Vesicles: A Future Challenging Milestone

“…For example, Clos-Garcia et al reported an elevated level of the steroid hormone dehydroepiandrosterone sulphate (DHEAS) in urinary EVs from prostate cancer patients [83]. In addition, recently Lou et al identified four metabolites as potential markers for Severe Acute Pancreatitis (SAP) diagnosis, including eicosatrienoic acid (C20:3), thiamine triphosphate, 2-Acetylfuran, and cis-Citral [84]. Beyond clinical applications, EVs metabolome might also provide alternative information on EVs as metabolically active machines.…”

“…The other encouraging application of lipidomics is the research of EVs lipid biomarkers. For example, Zhao et al investigated plasma derived-EVs lipidomes of women in the early second trimester with preterm and fully-term births [92], while Luo et al focused on the identification of potential metabolites biomarkers in pleural effusion-derived EVs for the rapid and correct diagnosis of tuberculosis pleural effusion (TPE) and malignancy pleural effusion (MPE) through both a metabolomic and lipidomic approach [84]. Nowadays, EVs represent wonderful candidates for novel ground-breaking drug delivery systems and for this reason, EVs lipidomics deals with an important challenge.…”

Identification of circulating extracellular vesicle long RNAs as diagnostic biomarkers for patients with severe acute pancreatitis

“…The top 20 differential mRNAs and top 20 differential lncRNAs were selected as the main research objects (Table S4 ), and the differential metabolites was recognised based on our previous work (Table S5 ). 8 Figure 4A visually shows the correlation heatmap between differential metabolites and differential genes obtained by the Spearman algorithm, showing the strong positive connections between transcriptomics and metabolomics. Via co‐enrichment analysis, we subsequently obtained the significant interconnections between genes and metabolites (Figure 4B ), pointing to the common pathways of tyrosine metabolism, gap junction, Parkinson's disease, and phenylalanine metabolism.…”