| Title: | Identification of Pre-Diagnostic Protein Biomarkers for Liver Cirrhosis Based on Prospective Analysis of a Large-Scale Plasma Proteomics in the UK Biobank |
| Journal: | Proteomics Clinical Applications |
| Published: | 13 Aug 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42592821/ |
| DOI: | https://doi.org/10.1002/prca.70050 |
| URL: | https://pmc.ncbi.nlm.nih.gov/articles/PMC13470838/pdf/PRCA-20-e70050.pdf |
Publication 21016
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Abstract
PURPOSE: Liver fibrosis and cirrhosis represent critical stages in the progression of chronic liver disease, yet their key molecular features remain incompletely understood.</p>
EXPERIMENTAL DESIGN: We performed large-scale Olink-based proteomic profiling in over 40,000 participants from the UK Biobank with a median follow-up of 15.6 years to elucidate disease pathophysiology and identify pre-diagnostic biomarkers. Cross-sectional analysis included 66 prevalent cirrhosis cases, and prospective analysis identified 224 incident cirrhosis cases. Machine learning and Mendelian randomization (MR) were applied. An independent cohort was used for validation.</p>
RESULTS: Distinct dysregulated proteins were observed in compensated cirrhosis (CC) and decompensated cirrhosis (DC). In the prospective analysis, 696 proteins were associated with disease onset. A proteomic panel based on these markers achieved an AUC of 0.832 for predicting incident cirrhosis, outperforming established fibrosis scores including FIB-4, APRI, and NFS, and demonstrated robust performance across CC and DC populations. The protein panel showed predictive value (AUC = 0.743) for disease progression in an independent cohort. MR identified 66 proteins with putative causal roles, including 11 potential therapeutic targets.</p>
CONCLUSIONS AND CLINICAL RELEVANCE: These findings provide novel molecular insights into cirrhosis development and support integrated proteomic biomarkers as a discovery and prioritization framework for early risk stratification.</p>
12 Keywords
- Biological Specimen Banks
- Biomarkers
- Cross-Sectional Studies
- Female
- Humans
- Liver Cirrhosis
- Male
- Middle Aged
- Prospective Studies
- Proteomics
- UK Biobank
- United Kingdom
11 Authors
- Jitian He
- Bo Li
- Yuping Yan
- Yajie Wang
- Mingxi Zhang
- Renyuan Sun
- Baohua Hou
- Shanzhou Huang
- Limin Zhen
- Dongping Wang
- Chuanzhao Zhang
1 Application
| Application ID | Title |
|---|---|
| 105314 | Investigating the genetics, lifestyles, environmental and clinical determinants and their interaction on development of hepatobiliary and pancreatic diseases/cancers. |
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