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DIA-based proteomics analysis of serum-derived exosomal proteins as potential candidate biomarkers for intrahepatic cholestasis in pregnancy

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

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 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.

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.

Results

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.

Conclusions

This preliminary work provides a better understanding of the proteomic alterations in the serum exosomes of pregnant women with ICP.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was financially supported by the Science and Technology Project of Jiangxi Province (grant nos. 20212BAB216065 and 20212BAG70006).

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Author notes

  1. Liju Nie and Siming Xin are contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics, Jiangxi Provincial Maternal and Child Health Hospital, 318 Bayi Avenue, 330006 Jiangxi Province, Nanchang, China

    Liju Nie, Siming Xin, Jiusheng Zheng, Huayan Chen, Xiaozhen Lei, Xiaoming Zeng & Hua Lai

  2. Key Laboratory of Women’s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, China

    Yong Luo, Yang Zou & Xianxian Liu

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  1. Liju Nie
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  2. Siming Xin
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Contributions

NLJ manuscript draft and interpretation. XSM experiments perform. ZJS oversaw the study design. LY data analysis. ZY and LXX text revision. CHY and LXZ samples and clinical data collect. ZXM and LH design, text revision and final approval.

Corresponding authors

Correspondence to Xiaoming Zeng or Hua Lai.

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Conflict of interest

None of the authors declare a conflict of interest of any kind.

Ethical statement

This study was approved by the Ethics Committee of Jiangxi Provincial Maternal and Child Health Hospital (registration number: EC-KT-202204 and EC-KT-202206, registered on January 5, 2022).

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Informed consent was obtained from patients.

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Nie, L., Xin, S., Zheng, J. et al. DIA-based proteomics analysis of serum-derived exosomal proteins as potential candidate biomarkers for intrahepatic cholestasis in pregnancy. Arch Gynecol Obstet 308, 79–89 (2023). https://doi.org/10.1007/s00404-022-06703-0

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