1. Multidimensional Proteomics Analysis of Amniotic Fluid to Provide Insight into the Mechanisms of Idiopathic Preterm Birth
- Author
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Stephen F. Thung, Sonya S. Abdel-Razeq, Victor A. Rosenberg, Guomao Zhao, Irina A. Buhimschi, and Catalin S. Buhimschi
- Subjects
Adult ,Proteomics ,Amniotic fluid ,Preterm labor ,Proteome ,Placenta ,lcsh:Medicine ,Down-Regulation ,Hemorrhage ,Biology ,Pregnancy Proteins ,Umbilical cord ,Umbilical Cord ,Pregnancy ,medicine ,Obstetrics/Preterm Labor ,Humans ,Electrophoresis, Gel, Two-Dimensional ,RNA, Messenger ,lcsh:Science ,Inflammation ,Multidisciplinary ,lcsh:R ,Preterm Births ,medicine.disease ,Amniotic Fluid ,Up-Regulation ,medicine.anatomical_structure ,Treatment Outcome ,Premature birth ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Immunology ,Etiology ,Premature Birth ,lcsh:Q ,Female ,Pharmacology/Personalized Medicine ,Biomarkers ,Software ,Research Article - Abstract
Background Though recent advancement in proteomics has provided a novel perspective on several distinct pathogenetic mechanisms leading to preterm birth (inflammation, bleeding), the etiology of most preterm births still remains elusive. We conducted a multidimensional proteomic analysis of the amniotic fluid to identify pathways related to preterm birth in the absence of inflammation or bleeding. Methodology/Principal Findings A proteomic fingerprint was generated from fresh amniotic fluid using surface-enhanced laser desorbtion ionization time of flight (SELDI-TOF) mass spectrometry in a total of 286 consecutive samples retrieved from women who presented with signs or symptoms of preterm labor or preterm premature rupture of the membranes. Inflammation and/or bleeding proteomic patterns were detected in 32% (92/286) of the SELDI tracings. In the remaining tracings, a hierarchical algorithm was applied based on descriptors quantifying similarity/dissimilarity among proteomic fingerprints. This allowed identification of a novel profile (Q-profile) based on the presence of 5 SELDI peaks in the 10–12.5 kDa mass area. Women displaying the Q-profile (mean±SD, gestational age: 25±4 weeks, n = 40) were more likely to deliver preterm despite expectant management in the context of intact membranes and normal amniotic fluid clinical results. Utilizing identification-centered proteomics techniques (fluorescence two-dimensional differential gel electrophoresis, robotic tryptic digestion and mass spectrometry) coupled with Protein ANalysis THrough Evolutionary Relationships (PANTHER) ontological classifications, we determined that in amniotic fluids with Q-profile the differentially expressed proteins are primarily involved in non-inflammatory biological processes such as protein metabolism, signal transduction and transport. Conclusion/Significance Proteomic profiling of amniotic fluid coupled with non-hierarchical bioinformatics algorithms identified a subgroup of patients at risk for preterm birth in the absence of intra-amniotic inflammation or bleeding, suggesting a novel pathogenetic pathway leading to preterm birth. The altered proteins may offer opportunities for therapeutical intervention and future drug development to prevent prematurity.
- Published
- 2008