Proteomic analysis of amniotic fluid for the identification of novel biomarkers and mechanisms related to preterm birth in the absence of infection/inflammation in women with preterm labor = Proteomic analysis of amniotic fluid for the identification of novel biomarkers and mechanisms related to preterm birth in the absence of infection/inflammation in women with preterm labor

다국어 초록 (Multilingual Abstract)

Objective: We aimed to comprehensively identify amniotic fluid (AF) biomarkers relating to spontaneous preterm delivery (SPTD) in the absence of intra-uterine infection/inflammation in women with preterm labor (PTL) and to demonstrate specific protein pathways that are activated in these cases.
Methods: This retrospective cohort study included 139 singleton pregnant women with PTL (24-32 weeks) who underwent amniocentesis and who showed no evidence of infection and/or inflammation. Label-free liquid chromatography-tandem mass spectrometry was used to identify AF proteins in pooled samples (n = 20) using a nested case-control approach. The six candidate biomarkers of interest were validated by enzyme-linked immunosorbent assays (ELISA) in the final cohort (n = 139). The differentially expressed proteins were analyzed by pathway analysis software. The primary outcome measure was SPTD before 34 weeks and SPTD within 14 days of sampling, respectively.
Results: Seventy-seven proteins were differentially expressed (p < 0.05) in AF from SPTD cases and term delivery controls, of which 48 (62.3%) were up-regulated and 29 (37.6%) were down-regulated. Validation by ELISA confirmed that AF from women who spontaneously deliverered preterm contained significantly lower levels of vascular endothelial growth factor receptor 1 (VEGFR1), and higher levels of insulin-like growth factor-binding protein-4 (IGFBP-4), lipocalin-2, and Fc fragment of IgG binding protein (FCGBP). The five pathways with the most differentially regulated proteins were glycolysis, gluconeogenesis, iron homeostasis signaling pathway, endoplasmic reticulum stress pathway, insulin-like growth factor 1 signaling.
Conclusion: Among women with PTL, proteomic analyses of AF identified four novel biomarkers (i.e., FCGBP, IGFBP-4, lipocalin-2, and VEGFR1) and specific protein pathways associated with SPTD in the absence of intra-uterine infection/inflammation. These altered proteins in AF may offer potential therapeutic targets to prevent SPTD.