IADR Abstract Archives
Salivary Proteomics Identifies Biomarkers for Early Detection of Pregnancy Loss
Objectives: Early pregnancy loss (EPL) within the first trimester, is one of the most common complications encountered in clinical practice. As most of EPLs occur quite early on during pregnancy, they are often ignored and misunderstood as an expected menstrual cycle. Thus, it is essential to investigate diagnostic biomarkers for monitoring pregnancy loss. Saliva collection being non-invasive becomes well suited for continuous non-invasive monitoring of EPL. Hence, we conducted a case-control study using iTRAQ-based proteomic approach to identify analytes that may act as biomarkers for non-invasive monitoring of subjects with risk of pregnancy loss.
Methods: Saliva samples were collected from a cohort of Singaporean Chinese pregnant women with EPL and matched cohort of healthy pregnant women as controls. Salivary proteins were extracted and subjected to iTRAQ-labeling and LC-MS/MS analysis. Peptide identification and quantification was done to identify the differentially abundant proteins in EPL. The iTRAQ data set were further validated using Enzyme-linked immunoassay (ELISA).
Results: Enrichment analysis of the 38 differentially abundant proteins identified that regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism were significantly affected in EPL patients. Gene ontology analysis revealed nucleosome assembly was significantly downregulated in EPL patients and was associated with depletion of histone proteins (H2B, H3 and H4). ELISA experiments confirmed that the expression of the histone proteins was consistent with the proteomic results. These data suggest that a depletion of histones can impairs nucleosome assembly. Regulation of nucleosome is critical for the maintenance of genome stability and epigenetic information, lack of which may lead to pregnancy loss.
Conclusions: Assessing and monitoring salivary histone levels in patients with threatened miscarriage can be a quick and easy method of obtaining periodic diagnostic information that can speed up treatment decisions.
Methods: Saliva samples were collected from a cohort of Singaporean Chinese pregnant women with EPL and matched cohort of healthy pregnant women as controls. Salivary proteins were extracted and subjected to iTRAQ-labeling and LC-MS/MS analysis. Peptide identification and quantification was done to identify the differentially abundant proteins in EPL. The iTRAQ data set were further validated using Enzyme-linked immunoassay (ELISA).
Results: Enrichment analysis of the 38 differentially abundant proteins identified that regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism were significantly affected in EPL patients. Gene ontology analysis revealed nucleosome assembly was significantly downregulated in EPL patients and was associated with depletion of histone proteins (H2B, H3 and H4). ELISA experiments confirmed that the expression of the histone proteins was consistent with the proteomic results. These data suggest that a depletion of histones can impairs nucleosome assembly. Regulation of nucleosome is critical for the maintenance of genome stability and epigenetic information, lack of which may lead to pregnancy loss.
Conclusions: Assessing and monitoring salivary histone levels in patients with threatened miscarriage can be a quick and easy method of obtaining periodic diagnostic information that can speed up treatment decisions.