Quantitative proteomic analysis of serum-purified exosomes identifies putative pre-eclampsia-associated biomarkers

Clinical Proteomics

José Luis Bartha¹  Ignacio Herraiz²  Alberto Galindo²  Fernando Corrales³  Rosana Navajas³  Alberto Paradela³  Antonio Ramos-Fernandez⁴ 

[1] Division of Obstetrics and Maternal Fetal Medicine, La Paz University Hospital, Madrid, Spain;Fetal Medicine Unit, Maternal and Child Health and Development Network (SAMID), Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain;Functional Proteomics Facility, Centro Nacional de Biotecnología (CNB-CSIC), ProteoRed-ISCIII, Madrid, Spain;Proteobotics, Madrid, Spain;

关键词: Biomarkers;    Cohort studies;    Exosome;    Mass spectrometry;    Plasma;    Pre-eclampsia;    Pregnancy;    Proteomics;    Serum;   

DOI  :  10.1186/s12014-022-09342-4

来源: Springer

【 摘 要 】

BackgroundThe high incidence of pre-eclampsia, which affects 2–7% of all pregnancies, remains a major health concern. Detection of pre-eclampsia before the appearance of clinical symptoms is essential to allow early intervention, and would benefit from identification of plasma/serum biomarkers to help guide diagnosis and treatment. Liquid biopsy has emerged as a promising source of protein biomarkers that circumvents some of the inherent challenges of proteome-wide analysis of plasma/serum. In this respect, purified exosomes have the added benefit of being carriers of intercellular communication both in physiological and pathological conditions.MethodsWe compared the protein complement of purified exosomes from three different collections of control and pre-eclamptic serum samples, obtained at the end of the second trimester of pregnancy and at delivery. We employed shotgun label-free proteomics to investigate differential protein expression, which was then validated by targeted proteomics.ResultsWe developed a purification method that yielded highly enriched exosome preparations. The presence of specific pregnancy protein markers suggested that a significant proportion of purified exosomes derived from tissues related to pregnancy. Quantitative proteomic analyses allowed us to identify 10, 114 and 98 differentially-regulated proteins in the three sample collections, with a high degree of concordance. Functional analysis suggested that these proteins participate in biological processes related to pre-eclampsia, including angiogenesis, inflammation and cell migration. The differential abundance of 66 proteins was validated by targeted proteomics. Finally, we studied the impact of the pre-eclampsia-associated exosomes in the proteome using an in vitro cellular model.ConclusionsWe have identified and validated differential exosomal proteins in liquid biopsy of pregnant women that open new possibilities for early detection of pre-eclampsia. Additionally, the functional impact of the proteome composition of purified pre-eclamptic exosomes in target cells provides new information to better understand changes in embryo-maternal interactions and, consequently, the pathogenesis of this disease.

【 授权许可】

CC BY