Validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia

OBJECTIVE: To demonstrate and validate the improvement of current risk stratification for bronchopulmonary dysplasia (BPD) early after birth by plasma protein markers (sialic acid-binding Ig-like lectin 14 (SIGLEC-14), basal cell adhesion molecule (BCAM), angiopoietin-like 3 protein (ANGPTL-3)) in e...

Descripción completa

Detalles Bibliográficos
Autores principales: Kindt, Alida S. D., Förster, Kai M., Cochius-den Otter, Suzan C. M., Flemmer, Andreas W., Hauck, Stefanie M., Flatley, Andrew, Kamphuis, Juliette, Karrasch, Stefan, Behr, Jürgen, Franz, Axel, Härtel, Christoph, Krumsiek, Jan, Tibboel, Dick, Hilgendorff, Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988689/
https://www.ncbi.nlm.nih.gov/pubmed/35595912
http://dx.doi.org/10.1038/s41390-022-02093-w
_version_ 1784901621398896640
author Kindt, Alida S. D.
Förster, Kai M.
Cochius-den Otter, Suzan C. M.
Flemmer, Andreas W.
Hauck, Stefanie M.
Flatley, Andrew
Kamphuis, Juliette
Karrasch, Stefan
Behr, Jürgen
Franz, Axel
Härtel, Christoph
Krumsiek, Jan
Tibboel, Dick
Hilgendorff, Anne
author_facet Kindt, Alida S. D.
Förster, Kai M.
Cochius-den Otter, Suzan C. M.
Flemmer, Andreas W.
Hauck, Stefanie M.
Flatley, Andrew
Kamphuis, Juliette
Karrasch, Stefan
Behr, Jürgen
Franz, Axel
Härtel, Christoph
Krumsiek, Jan
Tibboel, Dick
Hilgendorff, Anne
author_sort Kindt, Alida S. D.
collection PubMed
description OBJECTIVE: To demonstrate and validate the improvement of current risk stratification for bronchopulmonary dysplasia (BPD) early after birth by plasma protein markers (sialic acid-binding Ig-like lectin 14 (SIGLEC-14), basal cell adhesion molecule (BCAM), angiopoietin-like 3 protein (ANGPTL-3)) in extremely premature infants. METHODS AND RESULTS: Proteome screening in first-week-of-life plasma samples of n = 52 preterm infants <32 weeks gestational age (GA) on two proteomic platforms (SomaLogic(®), Olink-Proteomics(®)) confirmed three biomarkers with significant predictive power: BCAM, SIGLEC-14, and ANGPTL-3. We demonstrate high sensitivity (0.92) and specificity (0.86) under consideration of GA, show the proteins’ critical contribution to the predictive power of known clinical risk factors, e.g., birth weight and GA, and predicted the duration of mechanical ventilation, oxygen supplementation, as well as neonatal intensive care stay. We confirmed significant predictive power for BPD cases when switching to a clinically applicable method (enzyme-linked immunosorbent assay) in an independent sample set (n = 25, p < 0.001) and demonstrated disease specificity in different cohorts of neonatal and adult lung disease. CONCLUSION: While successfully addressing typical challenges of clinical biomarker studies, we demonstrated the potential of BCAM, SIGLEC-14, and ANGPTL-3 to inform future clinical decision making in the preterm infant at risk for BPD. TRIAL REGISTRATION: Deutsches Register Klinische Studien (DRKS) No. 00004600; https://www.drks.de. IMPACT: The urgent need for biomarkers that enable early decision making and personalized monitoring strategies in preterm infants with BPD is challenged by targeted marker analyses, cohort size, and disease heterogeneity. We demonstrate the potential of the plasma proteins BCAM, SIGLEC-14, and ANGPTL-3 to identify infants with BPD early after birth while improving the predictive power of clinical variables, confirming the robustness toward proteome assays and proving disease specificity. Our comprehensive analysis enables a phase-III clinical trial that allows full implementation of the biomarkers into clinical routine to enable early risk stratification in preterms with BPD.
format Online
Article
Text
id pubmed-9988689
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group US
record_format MEDLINE/PubMed
spelling pubmed-99886892023-03-08 Validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia Kindt, Alida S. D. Förster, Kai M. Cochius-den Otter, Suzan C. M. Flemmer, Andreas W. Hauck, Stefanie M. Flatley, Andrew Kamphuis, Juliette Karrasch, Stefan Behr, Jürgen Franz, Axel Härtel, Christoph Krumsiek, Jan Tibboel, Dick Hilgendorff, Anne Pediatr Res Clinical Research Article OBJECTIVE: To demonstrate and validate the improvement of current risk stratification for bronchopulmonary dysplasia (BPD) early after birth by plasma protein markers (sialic acid-binding Ig-like lectin 14 (SIGLEC-14), basal cell adhesion molecule (BCAM), angiopoietin-like 3 protein (ANGPTL-3)) in extremely premature infants. METHODS AND RESULTS: Proteome screening in first-week-of-life plasma samples of n = 52 preterm infants <32 weeks gestational age (GA) on two proteomic platforms (SomaLogic(®), Olink-Proteomics(®)) confirmed three biomarkers with significant predictive power: BCAM, SIGLEC-14, and ANGPTL-3. We demonstrate high sensitivity (0.92) and specificity (0.86) under consideration of GA, show the proteins’ critical contribution to the predictive power of known clinical risk factors, e.g., birth weight and GA, and predicted the duration of mechanical ventilation, oxygen supplementation, as well as neonatal intensive care stay. We confirmed significant predictive power for BPD cases when switching to a clinically applicable method (enzyme-linked immunosorbent assay) in an independent sample set (n = 25, p < 0.001) and demonstrated disease specificity in different cohorts of neonatal and adult lung disease. CONCLUSION: While successfully addressing typical challenges of clinical biomarker studies, we demonstrated the potential of BCAM, SIGLEC-14, and ANGPTL-3 to inform future clinical decision making in the preterm infant at risk for BPD. TRIAL REGISTRATION: Deutsches Register Klinische Studien (DRKS) No. 00004600; https://www.drks.de. IMPACT: The urgent need for biomarkers that enable early decision making and personalized monitoring strategies in preterm infants with BPD is challenged by targeted marker analyses, cohort size, and disease heterogeneity. We demonstrate the potential of the plasma proteins BCAM, SIGLEC-14, and ANGPTL-3 to identify infants with BPD early after birth while improving the predictive power of clinical variables, confirming the robustness toward proteome assays and proving disease specificity. Our comprehensive analysis enables a phase-III clinical trial that allows full implementation of the biomarkers into clinical routine to enable early risk stratification in preterms with BPD. Nature Publishing Group US 2022-05-20 2023 /pmc/articles/PMC9988689/ /pubmed/35595912 http://dx.doi.org/10.1038/s41390-022-02093-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Clinical Research Article
Kindt, Alida S. D.
Förster, Kai M.
Cochius-den Otter, Suzan C. M.
Flemmer, Andreas W.
Hauck, Stefanie M.
Flatley, Andrew
Kamphuis, Juliette
Karrasch, Stefan
Behr, Jürgen
Franz, Axel
Härtel, Christoph
Krumsiek, Jan
Tibboel, Dick
Hilgendorff, Anne
Validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia
title Validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia
title_full Validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia
title_fullStr Validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia
title_full_unstemmed Validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia
title_short Validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia
title_sort validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia
topic Clinical Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988689/
https://www.ncbi.nlm.nih.gov/pubmed/35595912
http://dx.doi.org/10.1038/s41390-022-02093-w
work_keys_str_mv AT kindtalidasd validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT forsterkaim validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT cochiusdenottersuzancm validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT flemmerandreasw validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT hauckstefaniem validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT flatleyandrew validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT kamphuisjuliette validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT karraschstefan validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT behrjurgen validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT franzaxel validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT hartelchristoph validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT krumsiekjan validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT tibboeldick validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia
AT hilgendorffanne validationofdiseasespecificbiomarkersfortheearlydetectionofbronchopulmonarydysplasia