Characterizing the urinary proteome of prematurity-associated lung disease in school-aged children.

Autor: Course CW; Department of Child Health, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK., Lewis PA; Proteomics Facility, Faculty of Life Sciences, University of Bristol, Bristol, UK., Kotecha SJ; Department of Child Health, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK., Cousins M; Department of Child Health, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.; Department of Paediatrics, Cardiff and Vale University Health Board, Cardiff, UK., Hart K; Department of Paediatrics, Cardiff and Vale University Health Board, Cardiff, UK., Watkins WJ; Department of Child Health, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK., Heesom KJ; Proteomics Facility, Faculty of Life Sciences, University of Bristol, Bristol, UK., Kotecha S; Department of Child Health, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK. kotechas@cardiff.ac.uk.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2023 Jul 20; Vol. 24 (1), pp. 191. Date of Electronic Publication: 2023 Jul 20.
DOI: 10.1186/s12931-023-02494-3
Abstrakt: Introduction: Although different phenotypes of lung disease after preterm birth have recently been described, the underlying mechanisms associated with each phenotype are poorly understood. We, therefore, compared the urinary proteome for different spirometry phenotypes in preterm-born children with preterm- and term-born controls.
Methods: Preterm and term-born children aged 7-12 years, from the Respiratory Health Outcomes in Neonates (RHiNO) cohort, underwent spirometry and urine collection. Urine was analysed by Nano-LC Mass-Spectrometry with Tandem-Mass Tag labelling. The preterm-born children were classified into phenotypes of prematurity-associated preserved ratio impaired spirometry (pPRISm, FEV 1  < lower limit of normal (LLN), FEV 1 /FVC ≥ LLN), prematurity-associated obstructive lung disease (POLD, FEV 1  < LLN, FEV 1 /FVC < LLN) and preterm controls (FEV 1  ≥ LLN,). Biological relationships between significantly altered protein abundances were analysed using Ingenuity Pathways Analysis software, and receiver operator characteristic curves were calculated.
Results: Urine was analysed from 160 preterm-born children and 44 term controls. 27 and 21 were classified into the pPRISm and POLD groups, respectively. A total of 785 proteins were detected. Compared to preterm-born controls, sixteen significantly altered proteins in the pPRISm group were linked to six biological processes related to upregulation of inflammation and T-cell biology. In contrast, four significantly altered proteins in the POLD group were linked with neutrophil accumulation. Four proteins (DNASE1, PGLYRP1, B2M, SERPINA3) in combination had an area under the curve of 0.73 for pPRISm and three combined proteins (S100A8, MMP9 and CTSC) had AUC of 0.76 for POLD.
Conclusions: In this exploratory study, we demonstrate differential associations of the urinary proteome with pPRISm and POLD.
Trial Registration: EudraCT: 2015-003712-20.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje