Abstract / Summary
Background Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality. Valid prognostic biomarkers are required to refine risk stratification and improve clinical management. This study aimed to identify potential prognostic biomarkers for predicting clinical outcomes in ACLF patients. Methods Seventy-four ACLF patients admitted to the Affiliated Hospital of Southwest Medical University between January 2021 and April 2022 were enrolled for retrospective analysis of baseline characteristics, clinical parameters and clinical outcomes. Forty patients were randomly selected for data-independent acquisition mass spectrometry (DIA-MS)-based proteomic profiling and differential protein analysis, and categorized into survival (n = 20) and non-survival (n = 20) groups according to 90-day outcomes. Bioinformatics analyses were performed to characterize candidate targets. Apolipoprotein C1 (APOC1) levels were validated by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic performance and compare it with a newly established model, conventional biomarkers and existing scoring systems. Single-cell RNA sequencing was applied to determine the cellular source and distribution of APOC1, and molecular docking was performed to screen potential APOC1-targeted therapeutic agents. Results Proteomic analysis identified 41 differentially expressed proteins (DEPs). Protein–protein interaction network analysis revealed that APOC1 occupied a core hub position in the network. Functional enrichment analysis indicated that DEPs were mainly involved in lipid metabolism, lipoprotein clearance and cholesterol efflux. ELISA confirmed significantly higher plasma APOC1 levels in the survival group, suggesting a protective role. Comparative ROC analysis demonstrated favorable prognostic performance of APOC1. Incorporation of APOC1 into traditional scoring systems moderately improved predictive efficacy. Single-cell RNA sequencing further revealed that APOC1 was predominantly expressed in hepatic macrophages. Molecular docking showed strong binding affinities of APOC1 with saikosaponin D and resveratrol, with binding energies of −7.8 and −6.7 kcal/mol, respectively. Elevated plasma APOC1 was positively correlated with survival in ACLF patients. Conclusion Plasma APOC1 serves as a novel prognostic biomarker for ACLF. Integrating APOC1 into conventional scoring systems yields complementary prognostic value. Hepatic macrophages represent the primary cellular source of APOC1, and saikosaponin D and resveratrol are promising candidate agents targeting APOC1.