Plasma Extracellular Vesicles Contain Protein Biomarkers for Capturing Stages of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Preliminary Exploratory Study

作者：Yakun Li, Koen C. van Son, S. Serna-Salas, J. Wolters, N. Wassenaar, S. Driessen, A. L. Mak, A. V. Dijk, Veera Houttu, J. Witjes, Diona Zwirs, Michail Doukas, Joanne Verheij, R. Dullaart, H. Blokzijl, A. G. Holleboom, Han Moshage · 发表于：Biomolecules · 年份：2025 · DOI：10.3390/biom15111596 · 被引用次数：1 · 研究领域：Medicine

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing in both prevalence and severity, highlighting the need for non-invasive biomarkers to assess disease activity. Extracellular vesicles (EVs), which carry molecular cargo from their cells of origin, hold promise as accessible biomarkers. We performed proteomic profiling of plasma-derived EVs from 70 patients with MASLD to identify protein signatures associated with key histological features (steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and fibrosis). These proteins were subsequently correlated with magnetic resonance (MR)-based liver imaging. Plasma EV protein profile differed between mild (S1) and advanced steatosis (S3). H4C1, OIT3, and ANPEP were elevated in S3, while CCDC25 and KLHL41 were decreased (|log2 fold change| > 1, p < 0.05). KLHL41 had a weak-to-moderate correlation with proton density fat fraction (PDFF) (R = −0.34, p = 0.016). GP1BA was upregulated in MASH (log2 fold change = 1.13, p = 0.03) but showed weak correlation with cT1, an imaging parameter for steatohepatitis (R = 0.22, p = 0.173). In fibrosis, complement component 7 (C7) was elevated in advanced (≥F3) vs. mild fibrosis (<F2) (log2 fold change = 0.95, adjusted p = 0.002) and correlated with MR elastography-derived liver stiffness (R = 0.38, p = 0.004). The AUC of C7 for differentiating <F2 vs. ≥F2 and <F3 vs. ≥F3 was 0.80 (95% CI: 0.69–0.91) and 0.83 (95% CI: 0.72–0.93), respectively. In conclusion, pl...