Using proteomics to advance the search for potential biomarkers for preeclampsia: A systematic review and meta-analysis

Abstract

Background Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality worldwide. Although predictive multiparametric screening is being developed, it is not applicable to nulliparous women, and is not applied to low-risk women. As PE is considered a heterogenous disorder, it is unlikely that any single multiparametric screening protocol containing a small group of biomarkers could have the required accuracy to predict all PE subgroups. Given the etiology of PE is complex and not fully understood, it begs the question, whether the search for biomarkers based on the predominant view of impaired placentation involving factors predominately implicated in angiogenesis and inflammation, has been too limiting. Here we highlight the enormous potential of state-of-the-art, high-throughput proteomics, to provide a comprehensive and unbiased approach to biomarker identification. Methods and findings Our literature search identified 1336 articles; after review, 45 studies with proteomic data from PE women that were eligible for inclusion. From 710 proteins with altered abundance, we identified 13 common circulating proteins, some of which had not been previously considered as prospective biomarkers of PE. An additional search of the literature for original publications testing any of the 13 common proteins using non-proteomic techniques was also undertaken. Strikingly, 9 of these common proteins had been independently evaluated in PE studies as potential biomarkers. Conclusion This study highlights the potential of using high-throughput data sets, which are comprehensive and without bias, to identify a profile of proteins that may improve predictions of PE and understanding of its etiology. We bring to the attention of the medical and research communities that the strengths and advantages of using data from high-throughput studies for biomarker discovery would be increased dramatically, if first and second trimester samples were collected for proteomics, and if standardized guidelines for patient reporting and data collection were implemented.

Assessment of Placental Extracellular Vesicles-Associated Fas Ligand and TNF-Related Apoptosis-Inducing Ligand in Pregnancies Complicated by Early and Late Onset Preeclampsia

“…Pregnant women with EO-PE had less favorable obstetric results with high blood pressure levels (severity criterion), premature deliveries (gestation ≤ 36 weeks), and low birth weights, compared to controls and to LO-PE pregnant women. This is consistent with previous studies (Lok et al, 2008;Nguyen et al, 2019).…”

Human OMICs and Computational Biology Research in Africa: Current Challenges and Prospects

“…Proteomics. Numerous proteomic studies have provided evidence for the influence of ethnicity on protein expression (Cho et al, 2017;Kim et al, 2010;Nguyen et al, 2019). We are currently in what might be considered the ''golden age'' of proteomics, characterized by the creation of public proteomics databases, the development of structural analysis tools which predict variant effects, such as HUMA and PRIMO (Brown and Tastan Bishop, 2018;Hatherley et al, 2016), and the standardization of data submission under the Proteo-meXchange consortium (Vizcaíno et al, 2014 Egypt).…”

Proteomic analysis of the umbilical cord in fetal growth restriction and preeclampsia

“…Mass spectrometry-based proteomics has emerged as a promising high-throughput technology for identification of potential biomarker candidates for diseases. Recent reviews have highlighted the proteomic approaches that have been used to explore PreE, FGR and preterm birth [13][14][15]. This data has been complicated by a wide variety of techniques used and tissues analyzed.…”