Abstract
We sought to identify biomarkers in the amniotic fluid (AF) and specific signaling pathways related to spontaneous preterm delivery (SPTD, < 34 weeks) in women with preterm labor (PTL) without intra-uterine infection/inflammation (IUI). This was a retrospective cohort study of a total of 139 PTL women with singleton gestation (24 + 0 to 32 + 6 weeks) who underwent amniocentesis and who displayed no evidence of IUI. A nested case–control was conducted using pooled AF samples (n = 20) analyzed via label-free liquid chromatography-tandem mass spectrometry. In the total cohort, an ELISA validation study was performed for seven candidate proteins of interest. Proteomic analysis identified 77 differentially expressed proteins (DEPs, P < 0.05) in the AF from SPTD cases compared to term delivery controls. ELISA validation confirmed that women who had an SPTD before 34 weeks had significantly independently lower levels of VEGFR-1 and higher levels of lipocalin-2 and the Fc fragment of IgG binding protein in the AF. Five principle pathways associated with the 77 DEPs were identified, including glycolysis, gluconeogenesis, and iron homeostasis. The proteomic analysis data of AFs from women with PTL identified several novel biomarkers and specific protein pathways related to SPTD in the absence of IUI.
Highlights
We sought to identify biomarkers in the amniotic fluid (AF) and specific signaling pathways related to spontaneous preterm delivery (SPTD, < 34 weeks) in women with preterm labor (PTL) without intra-uterine infection/inflammation (IUI)
The purposes of this study were to comprehensively identify AF biomarkers related to SPTD in the absence of intra-uterine infection/inflammation (IUI) in women with PTL using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), and to explore specific signaling pathways that are activated in these cases
We excluded patients with findings associated to intra-uterine infection/inflammation, which were defined as the presence of at least one of the following based on previous studies: elevated AF interleukin (IL)-6 levels (≥ 1.0 ng/mL) or white blood cell (WBC) counts (≥ 50 cells/mm3), positive AF culture or presence of histologic c horioamnionitis[11,12,13,14,15], because the current study primarily focused on the non-infectious and non-inflammatory causes of SPTD
Summary
We sought to identify biomarkers in the amniotic fluid (AF) and specific signaling pathways related to spontaneous preterm delivery (SPTD, < 34 weeks) in women with preterm labor (PTL) without intra-uterine infection/inflammation (IUI). They revealed that potential biomarkers involved in idiopathic preterm labor and delivery included five SELDI peaks in amniotic fluid (AF) Q-profile, placenta villous hypermaturation and senescence-associated β-galactosidase activity in the placenta, and protein Z levels and FokI Vitamin D receptor polymorphism in maternal blood[6,7,8,9] These studies have limited their analyses to specific target proteins or to those identified from single mass peaks, thereby not reflecting the total of proteins involved in multiple and intricate pathways for idiopathic preterm labor and delivery. The purposes of this study were to comprehensively identify AF biomarkers related to SPTD in the absence of intra-uterine infection/inflammation (IUI) in women with PTL using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), and to explore specific signaling pathways that are activated in these cases
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