SILAC-Based Characterization of Plasma-Derived Extracellular Vesicles in Patients Undergoing Partial Hepatectomy

被引:1
|
作者
Resch, Ulrike [1 ,2 ]
Hackl, Hubert [3 ]
Pereyra, David [4 ]
Santol, Jonas [4 ]
Brunnthaler, Laura [1 ]
Probst, Joel [4 ]
Jankoschek, Anna Sofie [4 ]
Aiad, Monika [4 ]
Nolte, Hendrik [2 ]
Krueger, Marcus [2 ]
Starlinger, Patrick [3 ,4 ,5 ]
Assinger, Alice [1 ]
机构
[1] Med Univ Vienna, Ctr Physiol & Pharmacol, Dept Vasc Biol & Thrombosis Res, Schwarzspanierstr 17, A-1090 Vienna, Austria
[2] Univ Cologne, Cluster Excellence Cellular Stress Responses Aging, Prote Core Facil, Joseph Stelzmann Str 26, D-50931 Cologne, Germany
[3] Med Univ Innsbruck, Inst Bioinformat, Bioctr, Innrain 80, A-6020 Innsbruck, Austria
[4] Med Univ Vienna, Gen Hosp, Dept Surg, Wahringer Gurtel 18-20, A-1090 Vienna, Austria
[5] Mayo Clin, Dept Surg, Div Hepatobiliary & Pancreat Surg, Rochester, MN 55902 USA
基金
奥地利科学基金会;
关键词
liver regeneration; extracellular vesicles; proteomics; post-hepatectomy liver failure; SET ENRICHMENT ANALYSIS; EXOSOMES;
D O I
10.3390/ijms251910685
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Post-hepatectomy liver failure (PHLF) remains a significant risk for patients undergoing partial hepatectomy (PHx). Reliable prognostic markers and treatments to enhance liver regeneration are lacking. Plasma nanoparticles, including lipoproteins, exosomes, and extracellular vesicles (EVs), can reflect systemic and tissue-wide proteostasis and stress, potentially aiding liver regeneration. However, their role in PHLF is still unknown. Methods: Our study included nine patients with hepatocellular carcinoma (HCC) undergoing PHx: three patients with PHLF, three patients undergoing the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure, and three matched controls without complications after PHx. Patient plasma was collected before PHx as well as 1 and 5 days after. EVs were isolated by ultracentrifugation, and extracted proteins were subjected to quantitative mass spectrometry using a super-SILAC mix prepared from primary and cancer cell lines. Results: We identified 2625 and quantified 2570 proteins in the EVs of PHx patients. Among these, 53 proteins were significantly upregulated and 32 were downregulated in patients with PHLF compared to those without PHLF. Furthermore, 110 proteins were upregulated and 78 were downregulated in PHLF patients compared to those undergoing ALPPS. The EV proteomic signature in PHLF indicates significant disruptions in protein translation, proteostasis, and intracellular vesicle biogenesis, as well as alterations in proteins involved in extracellular matrix (ECM) remodelling and the metabolic and cell cycle pathways, already present before PHx. Conclusions: Longitudinal proteomic analysis of the EVs circulating in the plasma of human patients undergoing PHx uncovers proteomic signatures associated with PHLF, which reflect dying hepatocytes and endothelial cells and were already present before PHx.
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页数:14
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