B-268 Proteo-transcriptomics Analysis Reveals Novel Diagnostic Biomarkers for Liver Fibrosis

Abstract Background Early diagnosis and prompt intervention are crucial for the effective management of liver fibrosis. Currently, there is a lack of sensitive and specific non-invasive biomarkers, leading to continued reliance on the invasive liver biopsy, which carries inherent risks. Our aim was to identify new biomarkers for the early diagnosis of liver fibrosis by combining serum proteomics with transcriptomics of fibrotic liver tissue, thus improving diagnostic accuracy and patient outcomes. Methods This study included serum samples from 55 patients diagnosed with liver disease, categorized into four groups based on pathological liver fibrosis grades according to the Metavir scoring system: F1 (n = 18), F2 (n = 16), F3 (n = 10), and F4 (n = 11). Serum proteomics was performed using 4D-data-independent acquisition mass spectrometry (4D-DIA-MS). Public transcriptomics data from three different etiologies of liver fibrosis with Metavir scoring were used for analysis (GSE84044, GSE135251, and GSE130970). Patients were dichotomized into groups with and without significant fibrosis, defined as Metavir fibrosis stage F=2. Univariate and multivariate logistic regression analyses were conducted to screen for candidate serum protein biomarkers. Results Based on 4D-DIA-MS, a total of 3936 serum proteins were identified. Further differential analysis of serum proteins, combined with differential genes from liver tissue transcriptomics, led to the identification of five candidate proteins (THBS2, AEBP1, LTBP2, COL14A1, LOXL1), all of which were elevated in significant fibrosis stages. Functional enrichment and cellular localization analyses revealed that these proteins are secretory proteins involved in the formation of the extracellular matrix, suggesting they may participate in the progression of liver fibrosis. Through univariate and multivariate logistic regression, Adipocyte Enhancer-Binding Protein 1 (AEBP1) was identified as a potential diagnostic biomarker for liver fibrosis. Serum AEBP1 levels demonstrated excellent performance in diagnosing significant liver fibrosis (AUC = 0.893, P < 0.0001, accuracy 85.0%), and showed a positive correlation with the severity of liver fibrosis (r = 0.662, P < 0.0001). Further analysis of patient clinical data revealed that serum AEBP1 levels outperformed existing diagnostic models (FIB-4 AUC = 0.754, APRI AUC = 0.808). Conclusion This study used a combined proteomics-transcriptomics analysis to identify a serum protein, AEBP1, which demonstrated superior diagnostic performance for early liver fibrosis compared to traditional indicators such as FIB-4 and APRI, highlighting its potential clinical application value in liver fibrosis diagnosis. Acknowledgement: Zhaopei Guo is supported by the Graduate Academic Exchange Fund of Fujian Medical University.