Department of Obstetrics, Jiangxi Provincial Maternal and Child Health Hospital, 318 Bayi Avenue, 330006 Jiangxi Province, Nanchang, China.
Key Laboratory of Women's Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, China.
Arch Gynecol Obstet. 2023 Jul;308(1):79-89. doi: 10.1007/s00404-022-06703-0. Epub 2022 Jul 18.
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 identification 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.
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.
The 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 identified proteins were functionally related to specific 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-2-glycoprotein I, Zinc finger protein 238, CP protein and Ficolin-3 were all approximately 0.9, indicating the promising diagnostic value of these proteins.
This preliminary work provides a better understanding of the proteomic alterations in the serum exosomes of pregnant women with ICP.
数据非依赖性采集（DIA）是用于大规模数字定性和定量研究的最强大且可重复的蛋白质组学技术之一。本研究旨在使用蛋白质组学方法鉴定与对照组相比在妊娠肝内胆汁淤积症（ICP）妇女中过度或表达不足的生物标志物，并发现用于ICP 检测的潜在生物标志物组合。
参与者包括 11 例 ICP 患者和 11 例健康孕妇作为对照组。在招募时收集了临床特征数据和实验室生化数据。然后，使用基于数据非依赖性采集（DIA）的蛋白质组学方法来鉴定 ICP 患者和对照组血清外泌体中差异表达的蛋白质（DEPs）。最后，使用生物信息学分析来鉴定这些 DEPs 所涉及的相关过程。
蛋白质组学结果显示，ICP 孕妇和健康孕妇血清外泌体中有 162 个 DEP，其中 106 个上调，56 个下调。基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析表明，鉴定的蛋白质在功能上与特定的细胞过程有关，包括凋亡、脂质代谢、免疫反应和细胞增殖以及代谢紊乱，这表明这些可能是 ICP 发病机制的主要原因。同时，补体和凝血级联可能与 ICP 的发展密切相关。受试者工作特征曲线（ROC）分析显示，伸长因子 1-α 1、β-2-糖蛋白 I、锌指蛋白 238、CP 蛋白和纤维胶蛋白-3 的曲线下面积值均约为 0.9，表明这些蛋白质具有有希望的诊断价值。
这项初步工作更好地了解了妊娠妇女 ICP 血清外泌体的蛋白质组学改变。
