Gravida Serum POSTN and PAPPA as the Potential Biomarkers for Fetal Congenital Heart Disease Based on Quantitative and Qualitative Proteomics
Abstract Background: Fetal congenital heart disease is the most common congenital defect worldwide. It has some missed diagnoses and a lack of disease biomarkers. We aim to seek objective biomarkers for noninvasive prenatal diagnosis of fetal congenital heart disease to reduce the missed diagnosis and explore its mechanism,Methods: This study used data-independent acquisition and parallel reaction monitoring to explore potential protein biomarkers that co-exist in gravida serum and fetal amniotic fluid. Moreover, logistic regression and ROC curve to establish the diagnostic model of fetal congenital heart disease potential biomarkers and molecular biology experiments were performed to validate proteomics results and explore the mechanism. Results: Proteomics and bioinformatics results show that 12 proteins co-exist in gravida serum and amniotic fluid. We identified POSTN and PAPPA in GS as candidate biomarkers and established the diagnostic model with a sensitivity of 100%, a specificity of 95% and the AUC value of 0.968 to diagnose congenital heart disease. In addition, the results of ELISA, IHC, and RT-PCR were consistent with those of proteomics. Moreover, POSTN may involve in fetal congenital heart disease through the TGF-beta signaling pathway. Conclusion: It is the first time to find that POSTN and PAPPA in GS are related to fetal congenital heart disease, contributing to developing a novel noninvasive prenatal method to diagnose fetal congenital heart disease and reduce congenital disabilities.