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Background   Hepatic fibrosis is a severe liver disease that has threatened human health for a long time. In order to undergo timely and adequate therapy, it is important for patients to obtain an accurate diagnosis of fibrosis. Laboratory inspection methods have been efficient in distinguishing between advanced hepatic fibrosis stages (F3, F4), but the identification of early stages of fibrosis has not been achieved. The development of proteomics may provide us with a new direction to identify the stages of fibrosis.Methods   We established serum proteomic maps for patients with hepatic fibrosis at different stages and identified differential expression of proteins between fibrosis stages through ultra-high-performance liquid chromatography tandem mass spectrometry proteomic analysis.Results   From the proteomic profiles of the serum of patients with different stages of liver fibrosis, a total of 1,338 proteins were identified. Among three early fibrosis stages (control, F1, and F2), 55 differential proteins were identified, but no proteins simultaneously exhibited differential expression between control, F1, and F2. Differential proteins were detected in the comparison between different fibrosis stages. Significant differences were found between advanced fibrosis stages (F2-vs.-F3 and F3-vs.-F4) through a series of statistical analysis, including hierarchical clustering, Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction network analysis. The differential proteins identified by GO annotation were associated with biological processes (mainly platelet degranulation and cell adhesion), molecular functions, and cellular components.Conclusions   All potential biomarkers identified between the stages of fibrosis could be key points in determining the fibrosis staging. The differences between early stages may provide a useful reference in addressing the challenge of early fibrosis staging.

Proteomic Analysis of Human Serum for Patients at Different Pathological Stages of Hepatic Fibrosis