Proteomic analysis of serum extracellular vesicles reveals Fibulin-3 as a new marker predicting liver-related events in MASLD-Reference-Cited by-同舟云学术

Proteomic analysis of serum extracellular vesicles reveals Fibulin-3 as a new marker predicting liver-related events in MASLD

Published:2024-06 Issue:6 Volume:8 Page:
ISSN:2471-254X
Container-title:Hepatology Communications
language:en
Short-container-title:

Author:

Sakane Sadatsugu¹^ORCID,Hikita Hayato¹,Shirai Kumiko¹,Sakamoto Tatsuya¹,Narumi Ryohei²,Adachi Jun²,Kakita Naruyasu³,Yamada Yukinori³,Toyoda Hidenori⁴,Takahashi Hirokazu⁵,Suda Goki⁶,Kai Machiko¹,Tahata Yuki¹,Sakamori Ryotaro¹,Kumazaki Shusuke¹,Fukumoto Kenji¹,Myojin Yuta¹^ORCID,Murai Kazuhiro¹^ORCID,Kodama Takahiro¹^ORCID,Tatsumi Tomohide¹,Tomonaga Takeshi²,Sakamoto Naoya⁶,Morii Eiichi⁷,Takehara Tetsuo¹

Affiliation:

1. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka, Japan

2. Laboratory of Proteomics for Drug Discovery, Center for Drug Design Research, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan

3. Department of Gastroenterology and Hepatology, Kaizuka City Hospital, Osaka, Japan

4. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan

5. Liver Center, Saga University Hospital, Saga, Japan

6. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

7. Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan

Abstract

Background: There is a need for novel noninvasive markers for metabolic dysfunction–associated steatotic liver disease (MASLD) to stratify patients at high risk for liver-related events including liver cancer and decompensation. In the present study, we used proteomic analysis of proteins in extracellular vesicles (EVs) to identify new biomarkers that change with fibrosis progression and can predict the development of liver-related events. Methods: We analyzed serum EVs from 50 patients with MASLD assessed for liver fibrosis by biopsy and identified proteins that altered with advanced fibrosis. A further evaluation was conducted on another cohort of 463 patients with MASLD with biopsy. Results: Eight candidate proteins were identified by proteomic analysis of serum EVs. Among them, serum levels of Fibulin-3, Fibulin-1, and Ficolin 1 correlated with their EV levels. In addition, serum Fibulin-3 and serum Fibulin-1 levels changed significantly with advanced fibrosis. Using another cohort with biopsy, we found that the serum Fibulin-3 concentration was significantly greater in those with advanced fibrosis but that the serum Fibulin-1 concentration was not significantly different. Multivariate Cox proportional hazards analysis revealed that a higher Fibrosis-4 (FIB-4) index and higher serum Fibulin-3 concentration were independent risk factors for liver-related events. When the cutoff value for the serum Fibulin-3 concentration was 6.0 µg/mL according to the Youden index of AUROCs, patients with high serum Fibulin-3 significantly more frequently developed liver-related events than did other patients. Validation using another cohort of 226 patients with clinically diagnosed MASLD confirmed that high serum Fibulin-3 levels are associated with a greater frequency of liver-related events. Conclusions: Serum Fibulin-3 was identified as a biomarker for predicting liver-related events in patients with MASLD.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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