Identification of Gravida Serum Biomarkers for Noninvasive Prenatal Diagnosis Fetal Congenital Heart Disease

Congenital heart disease (CHD) is well established as the most common congenital defect worldwide. Given the lack of biomarkers available, we aimed to identify new biomarkers for the noninvasive prenatal diagnosis of fetal CHD. This study used data-independent acquisition (DIA) to explore potential protein biomarkers that co-expressed in gravida serum (GS) and fetal amniotic fluid (AF). Next, parallel reaction monitoring (PRM), enzyme-linked immunosorbent assay (ELISA), receiver operating characteristic curve (ROC) analysis, and the immunohistochemistry (IHC) were performed to validate the potential biomarkers. Based on DIA and PRM proteomics and bioinformatics results, we identified POSTN and PAPPA in GS as candidate biomarkers. Their differential expression during ELISA and IHC were generally consistent with our proteomics results. POSTN combined with PAPPA in GS yield a good diagnose fetal CHD with sensitivity of 83.9%, specificity of 73.9%, and an area under curve (AUC) of 0.842. This is the first study showing that POSTN in GS and AF is associated with fetal CHD. POSTN and PAPPA have huge prospects for application as potential biomarkers in the noninvasive prenatal diagnosis of fetal CHD. Graphical abstract Congenital heart disease (CHD) is well-established as the most common congenital defect worldwide. Given the lack of biomarkers available, we aimed to identify new biomarkers for the noninvasive prenatal diagnosis of fetal CHD. We used data independent acquisition (DIA) to explore potential protein biomarkers that co-expressed in gravida serum (GS) and fetal amniotic fluid (AF). Next, parallel reaction monitoring (PRM), enzyme-linked immunosorbent assay (ELISA), receiver operating characteristic curve (ROC) analysis, and the immunohistochemistry (IHC) were performed to validate the potential biomarkers. Based on DIA and PRM proteomics and bioinformatics results, we identified POSTN and PAPPA in GS as candidate biomarkers. Their differential expression during ELISA and IHC were generally consistent with our proteomics results. POSTN combined with PAPPA in GS yield a good diagnose fetal CHD with sensitivity of 83.9 %, specificity of 73.9%, and an area under curve (AUC) of 0.842. This is the first study showing that POSTN in GS and AF is associated with fetal CHD. POSTN and PAPPA have huge prospects for application as potential biomarkers in the noninvasive prenatal diagnosis of fetal CHD