Resch, U.; Hackl, H.; Pereyra, D.; Santol, J.; Brunnthaler, L.; Probst, J.; Jankoschek, A. S.; Aiad, M.; Nolte, H.; Krueger, M.; Starlinger, P.; Assinger, A. SILAC-Based Characterization of Plasma-Derived Extracellular Vesicles in Patients Undergoing Partial Hepatectomy. Preprints2024, 2024082181. https://doi.org/10.20944/preprints202408.2181.v1
APA Style
Resch, U., Hackl, H., Pereyra, D., Santol, J., Brunnthaler, L., Probst, J., Jankoschek, A. S., Aiad, M., Nolte, H., Krueger, M., Starlinger, P., & Assinger, A. (2024). SILAC-Based Characterization of Plasma-Derived Extracellular Vesicles in Patients Undergoing Partial Hepatectomy. Preprints. https://doi.org/10.20944/preprints202408.2181.v1
Chicago/Turabian Style
Resch, U., Patrick Starlinger and Alice Assinger. 2024 "SILAC-Based Characterization of Plasma-Derived Extracellular Vesicles in Patients Undergoing Partial Hepatectomy" Preprints. https://doi.org/10.20944/preprints202408.2181.v1
Abstract
Rationale: 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 unknow.
Methods: Our study included 9 patients with hepatocellular carcinoma (HCC) undergoing PHx: 3 patients with PHLF, 3 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 (PRE), 1 and 5 days (POD1, POD5) after PHx. EVs were isolated by ultracentrifugation and extracted proteins 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 EVs in 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 compared to patients undergoing ALPPS. The EV-proteomic signature in PHLF indicates significant disruptions in protein translation, proteostasis, intracellular vesicle biogenesis, as well as alterations in proteins involved in extracellular matrix (ECM) remodeling, metabolic and cell cycle pathways, present already before PHx.
Conclusion: Longitudinal proteomic analysis of EV´s circulating in human patient plasma undergoing PHx uncovers proteomic signatures associated with PHLF which reflect dying hepatocytes and endothelial cells and are present before PHx already. Our results support EVs as potential biomarkers and therapeutic targets for liver regeneration and failure.
Keywords
Liver regeneration; extracellular vesicles; biomarkers; proteomics; post hepatectomy liver failure
Subject
Biology and Life Sciences, Life Sciences
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
