Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Ιωάννα Ραχήλ Συνοδινού Traeger, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Δασκαλάκης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Καλλιόπη Παππά, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Μακάριος Ελευθεριάδης, Επίκουρος Καθηγητή, Ιατρική Σχολή, ΕΚΠΑ
Μαριάννα Θεοδώρα, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Παναγιώτης Αντσακλής, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Χρυσταλέννα Σοφοκλέους, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Πρωτεωμικοί δείκτες πρώιμης ανίχνευσης εγκύων υψηλού κινδύνου για πρόωρο τοκετό
Translated title:
Proteomic biomarkers for early detection of women at high risk for preterm labour
Summary:
Aim: To identify proteins related to the early prediction and the pathogenic mechanism of preterm delivery by examining their expression in the peripheral blood of pregnant women during the first trimester, who later experienced preterm delivery between 32/7 and 36/7 weeks of gestation, in comparison to women with full-term pregnancies.
Materials & Methods: In the exploratory phase of the study, protein expression analysis was conducted using proteomic methods, including high-performance liquid chromatography (HPLC) in combination with tandem mass spectrometry (MS/MS) and protein labeling with iTRAQ reagents, on plasma samples from 5 pregnant women with preterm delivery and 5 with full-term pregnancies (control group). Subsequently, proteins with differential expression between the two groups were analyzed using bioinformatics methods to identify the regulatory pathways involved, along with Gene Ontology analysis (biological process, molecular function, and cellular component).
In the validation phase of the study, differential expression of identified proteins from the exploratory phase was confirmed using targeted quantitative analysis of selected proteins via enzyme-linked immunosorbent assay (ELISA) in 58 peripheral blood samples, 29 from pregnant women who later experienced preterm delivery between 32/7 and 36/7 weeks, and 29 from pregnant women without complications.
Results: Comparative analysis of protein expression led to the identification of 142 proteins with differential expression between the two groups, among which 54 showed increased expression in pregnant women who ultimately gave birth prematurely at 32/7 and 36/7 weeks of gestation compared to the control group (fold change >1.5), while 88 showed decreased expression (fold change <0.5). No proteins with differentially expressed levels meeting the criteria for statistical significance (p<0.05) were detected. In silico analysis revealed that proteins with differential expression in the plasma of women with automatic preterm delivery are primarily enriched in the coagulation regulatory pathway and the complement pathway, confirming the involvement of the hemostatic system and complement activation in the pathogenic mechanism leading to the complication.
In the second stage of the study for further confirmation, three proteins - VCAM-1, SAA, and Talin-1 - were selected with the most significant p-value (lowest p-value). The analysis confirmed the findings of the proteomic analysis and revealed reduced levels of VCAM-1, SAA, and Talin-1 proteins in the plasma of pregnant women during the first trimester who subsequently experienced automatic preterm delivery. Statistical analysis demonstrated the ability to distinguish high-risk pregnant women for automatic preterm delivery from those with AUC>0.8 and p<0.05. According to the multivariate regression model, VCAM-1 (p=0.001) and Talin-1 (p<0.001) proteins can accurately predict subsequent automatic preterm delivery independently of the studied factors (history of automatic preterm delivery, smoking, BMI before pregnancy, maternal age, fetal gender, and method of conception).
Conclusion: In this study, the use of proteomic technology for studying protein expression in the peripheral blood of pregnant women during the first trimester led to the identification of Talin-1 and VCAM-1 proteins as potential biomarkers closely associated with the risk of automatic preterm delivery. These biomarkers, after evaluation in large-scale studies, may facilitate understanding of the pathophysiological mechanism of the complication and contribute to the development of specialized and cost-effective predictive tests that will revolutionize pregnancy management. Additionally, they represent potential therapeutic targets.
Main subject category:
Health Sciences
Keywords:
Pregnancy complications, Preterm labour, Preterm birth, Biomarkers, Proteomics
Number of references:
364
