Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses

Abstract

Background Preeclampsia remains a serious disorder that puts at risk the lives of perinatal mothers and infants worldwide. This study assessed potential pathogenic mechanisms underlying preeclampsia by investigating differentially expressed proteins (DEPs) in the serum of patients with early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) compared with healthy pregnant women. Methods Blood samples were collected from four women with EOPE, four women with LOPE, and eight women with normal pregnancies, with four women providing control samples for each preeclampsia group. Serum proteins were identified by isobaric tags for relative and absolute quantitation combined with liquid chromatography–tandem mass spectrometry. Serum proteins with differences in their levels compared with control groups of at least 1.2 fold-changes and that were also statistically significantly different between the groups at P < 0.05 were further analyzed. Bioinformatics analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses, were used to determine the key proteins and signaling pathways associated with the development of PE and to determine those DEPs that differed between women with EOPE and those with LOPE. Key protein identified by mass spectrometry was verified by enzyme linked immunosorbent assay (ELISA). Results Compared with serum samples from healthy pregnant women, those from women with EOPE displayed 70 proteins that were differentially expressed with significance. Among them, 51 proteins were significantly upregulated and 19 proteins were significantly downregulated. In serum samples from women with LOPE, 24 DEPs were identified , with 10 proteins significantly upregulated and 14 proteins significantly downregulated compared with healthy pregnant women. Bioinformatics analyses indicated that DEPs in both the EOPE and LOPE groups were associated with abnormalities in the activation of the coagulation cascade and complement system as well as with lipid metabolism. In addition, 19 DEPs in the EOPE group were closely related to placental development or invasion of tumor cells. Downregulationof pregnancy-specific beta-1-glycoprotein 9 (PSG9) in the LOPE group was confirmed by ELISA. Conclusion The pathogenesis of EOPE and LOPE appeared to be associated with coagulation cascade activation, lipid metabolism, and complement activation. However, the pathogenesis of EOPE also involved processes associated with greater placental injury. This study provided several new proteins in the serum which may be valuable for clinical diagnosis of EOPE and LOPE, and offered potential mechanisms underpinning the development of these disorders.