Comprehensive maternal serum proteomics identifies the cytoskeletal proteins as non-invasive biomarkers in prenatal diagnosis of congenital heart defects

Abstract

Congenital heart defects (CHDs) are the most common group of major birth defects. Presently there are no clinically used biomarkers for prenatally detecting CHDs. Here, we performed a comprehensive maternal serum proteomics assessment, combined with immunoassays, for the discovery of non-invasive biomarkers for prenatal diagnosis of CHDs. A total of 370 women were included in this study. An isobaric tagging for relative and absolute quantification (iTRAQ) proteomic approach was used first to compare protein profiles in pooled serum collected from women who had CHD-possessing or normal fetuses, and 47 proteins displayed significant differential expressions. Targeted verifications were performed on 11 proteins using multiple reaction monitoring mass spectrometry (MRM-MS), and the resultant candidate biomarkers were then further validated using ELISA analysis. Finally, we identified a biomarker panel composed of 4 cytoskeletal proteins capable of differentiating CHD-pregnancies from normal ones [with an area under the receiver operating characteristic curve (AUC) of 0.938, P < 0.0001]. The discovery of cytoskeletal protein changes in maternal serum not only could help us in prenatal diagnosis of CHDs, but also may shed new light on CHD embryogenesis studies.

Proteomic profile of the Bradysia odoriphaga in response to the microbial secondary metabolite benzothiazole

“…Cytoskeletal proteins are involved in many vital metabolic processes, such as cellular polarity, cell elongation, division, endocytosis and vesicular trafficking4445. In our present study, the expression of two cytoskeleton-related proteins, actin-2 and calponin/transgelin, were up-regulated after exposure to benzothiazole.…”

Molecular Diagnostics and In Utero Therapeutics for Orofacial Clefts

“…Proteomic approaches have since arisen to better diagnose a range of chromosomal aberrations (Narasimhan et al 2013). More recent advances in prenatal diagnostics have involved putative protein biomarkers to discriminate normal pregnancies from those with congenital heart defects, with changes in protein levels having been identified from as early as 8 wk of gestation (Chen et al 2016). Interestingly, studied cardiac structural anomalies were polygenic in nature, which foreshadows that the diagnosis of clefts with diverse genetic diagnoses may be possible by appraisal of a handful of biomarkers from known cleft-associated pathways.…”

Analysis of the plasma proteome using iTRAQ and TMT‐based Isobaric labeling

“…164 Analysis of the plasma proteome in relation to potential birth and genetic defects have included the iTRAQ-based comparisons of plasma from mothers bearing Down syndrome fetuses with plasma from uncomplicated pregnancies, 167 and serum of pregnant women carrying a fetus with conotruncal heart defects. 81,168 Sui et al compared umbilical cord blood from mothers carrying Down syndrome fetuses (n = 6) and healthy fetuses (n = 11). Using iTRAQ labeling, SCX fractionation and LC-MALDI they identified 505 proteins and reported five putative biomarkers.…”