Serum proteomic profiling of patients with compensated advanced chronic liver disease with and without clinically significant portal hypertension

Scientific paper - Original scientific paper

• Author: Frane Paštrović
• Author: Ruđer Novak
• Author: Ivica Grgurević
• Author: Stela Hrkač
• Author: Grgur Salai
• Author: Marko Žarak
• Author: Lovorka Grgurević
• Author's institution: University of Zagreb; School of Medicine; (Department of Anatomy and Clinical Anatomy)
• Author's institution: University of Zagreb; School of Medicine; (Department of Internal Medicine)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Anatomy
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract (english)

Introduction: Portal hypertension (PH) drives the progression of liver cirrhosis to decompensation and death. Hepatic venous pressure gradient (HVPG) measurement is the standard of PH quantification, and HVPG≥10 mmHg defines clinically significant PH (CSPH). We performed proteomics-based serum profiling to search for a proteomic signature of CSPH in patients with compensated advanced chronic liver disease (cACLD).

Materials and methods: Consecutive patients with histologically confirmed cACLD and results of HVPG measurements were prospectively included. Serum samples were pooled according to the presence/absence of CSPH and analysed by liquid chromatography-mass spectrometry. Gene set enrichment analysis was performed, followed by comprehensive literature review for proteins identified with the most striking difference between the groups.

Results: We included 48 patients (30 with, and 18 without CSPH). Protein CD44, involved in the inflammatory response, vascular endothelial growth factor C (VEGF-C) and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), both involved in lymphangiogenesis were found solely in the CSPH group. Although identified in both groups, proteins involved in neutrophil extracellular traps (NET) formation, as well as tenascin C, autotaxin and nephronectin which mediate vascular contractility and lymphangiogenesis were more abundant in CSPH.

Discussion and conclusion: We propose that altered inflammatory response, including NET formation, vascular contractility and formation of new lymph vessels are key steps in PH development. Proteins such as CD44, VEGF-C, LYVE-1, tenascin C, Plasminogen activator inhibitor 1, Nephronectin, Bactericidal permeability-increasing protein, Autotaxin, Myeloperoxidase and a disintegrin and metalloproteinase with thrombospondin motifs-like protein 4 might be considered for further validation as potential therapeutic targets and candidate biomarkers of CSPH in cACLD.

• Keywords (english): Elasticity Imaging Techniques; Humans; Hypertension, Portal; Liver; Liver Cirrhosis; Portal Pressure; Proteomics; Tenascin; Vascular Endothelial Growth Factor C
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: PLOS ONE
• Numbering: vol. 19, no. 4, e0301416
• e-ISSN: 1932-6203
• DOI: https://doi.org/10.1371/journal.pone.0301416
• URN:NBN: urn:nbn:hr:105:159721
• Publication: 2024-04-11
• Project: Number: KK.01.1.1.01.0008; Title (croatian): Reproduktivna i regenerativna medicina - istraživanja novih platformi i potencijala; Title (english): Scientific Center of Excellence for Reproductive and Regenerative Medicine; Acronym: CERRM; Leader: Davor Ježek; Jurisdiction: eu; Funding stream: European Regional Development Fund
• Document URL: https://dx.plos.org/10.1371/journal.pone.0301416
• Type of resource: Text
• Access conditions: Open access
• Created on: 2025-03-13 08:00:56