Background Data-independent acquisition (DIA) is one of the most powerful and reproducible proteomic technologies for large-scale digital qualitative and quantitative research. The aim of this study was to use proteomic methodologies for the identi cation of biomarkers that are over-or underexpressed in women with intrahepatic cholestasis of pregnancy (ICP) compared with controls and discover a potential biomarker panel for ICP detection.Methods The participants included 11 ICP patients and 11 healthy pregnant women as controls. The clinical characteristic data and the laboratory biochemical data were collected at the time of recruitment. Then, a data-independent acquisition (DIA)-based proteomics approach was used to identify differentially expressed proteins (DEPs) in serum exosomes between ICP patients and controls. Finally, bioinformatics analysis was used to identify the relevant processes in which these DEPs were involved.
ResultsThe proteomics results showed that there were 162 DEPs in serum exosomes between pregnant women with ICP and healthy pregnant women, of which 106 were upregulated and 56 were downregulated in ICP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the identi ed proteins were functionally related to speci c cell processes including apoptosis, lipid metabolism, immune response and cell proliferation, and metabolic disorders, suggesting that these may be primary causative factors in ICP pathogenesis. Meanwhile, complement and coagulation cascades may be closely related to the development of ICP. Receiver operating characteristic curve (ROC) analysis showed that the area under the curve values of Elongation factor 1-alpha 1, Beta-2glycoprotein I, Zinc nger protein 238, CP protein and Ficolin-3 were all approximately 0.9, indicating the promising diagnostic value of these proteins.Conclusions This preliminary work provides a better understanding of the proteomic alterations in the serum exosomes of pregnant women with ICP and may provide new insights into ICP pathophysiology and potential novel treatment targets for this disease. However, future studies of the systemic expression of these candidate biomarkers and their exact roles in ICP will be essential for conformation of this hypothesis.