Identification of protein biomarkers associated with congenital diaphragmatic hernia in human amniotic fluid.
Autor: | Bhutada S; Department of Biomedical Engineering-ND20, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA., Tran-Lundmark K; Department of Experimental Medical Science and Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.; The Pediatric Heart Center, Skane University Hospital, Lund, Sweden., Kramer B; Department of Thoracic and Cardiovascular Surgery, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA., Conner P; Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden., Lowry AM; Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA., Blackstone E; Department of Thoracic and Cardiovascular Surgery, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.; Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA., Frenckner B; Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden., Mesas-Burgos C; Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden., Apte SS; Department of Biomedical Engineering-ND20, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. aptes@ccf.org. |
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Jazyk: | angličtina |
Zdroj: | Scientific reports [Sci Rep] 2023 Sep 19; Vol. 13 (1), pp. 15483. Date of Electronic Publication: 2023 Sep 19. |
DOI: | 10.1038/s41598-023-42576-2 |
Abstrakt: | Congenital diaphragmatic hernia (CDH) is a severe birth defect frequently associated with pulmonary hypoplasia, pulmonary hypertension, and heart failure. Since amniotic fluid comprises proteins of both fetal and maternal origin, its analysis could provide insights on mechanisms underlying CDH and provide biomarkers for early diagnosis, severity of pulmonary changes and treatment response. The study objective was to identify proteomic changes in amniotic fluid consistently associated with CDH. Amniotic fluid was obtained at term (37-39 weeks) from women with normal pregnancies (n = 5) or carrying fetuses with CDH (n = 5). After immuno-depletion of the highest abundance proteins, off-line fractionation and high-resolution tandem mass spectrometry were performed and quantitative differences between the proteomes of the groups were determined. Of 1036 proteins identified, 218 were differentially abundant. Bioinformatics analysis showed significant changes in GP6 signaling, in the MSP-RON signaling in macrophages pathway and in networks associated with cardiovascular system development and function, connective tissue disorders and dermatological conditions. Differences in selected proteins, namely pulmonary surfactant protein B, osteopontin, kallikrein 5 and galectin-3 were validated by orthogonal testing using ELISA in larger cohorts and showed statistically significant differences aiding in the diagnosis and prediction of CDH. The findings provide potential tools for clinical management of CDH. (© 2023. Springer Nature Limited.) |
Databáze: | MEDLINE |
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