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Vol. 61. Issue 2.
Pages 67-75 (February 2025)
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Vol. 61. Issue 2.
Pages 67-75 (February 2025)
Original Article
Quantitative Proteomics Analysis of Serum and Urine With DIA Mass Spectrometry Reveals Biomarkers for Pediatric Obstructive Sleep Apnea
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Yunxiao Wua, Mansheng Lib, Kai Zhangc, Jie Mab, David Gozald, Yunping Zhub,&#¿;
Corresponding author
zhuyunping@ncpsb.org.cn

Corresponding authors.
, Zhifei Xuc,&#¿;
Corresponding author
zhifeixu@aliyun.com

Corresponding authors.
a Department of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
b State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China
c Clinical Department of National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
d Office of the Dean, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
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Table 1. Clinical characteristics and PSG results.
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Abstract
Objectives

Identification of suitable biomarkers that facilitate the screening and evaluation of pediatric obstructive sleep apnea (OSA) and its severity was explored.

Methods

Data-independent acquisition quantitative proteomic analysis was employed to identify serum and urine proteins with differential expression patterns between children with OSA and controls. Differentially expressed proteins that gradually increased or decreased with the severity of OSA were retained as potential biomarkers and underwent ELISA validation.

Results

We found that with increasing severity of OSA, there was a gradual upregulation of 34 proteins in the serum and 124 proteins in the urine, along with a respective downregulation of 10 serum proteins and 64 urinary proteins in the initial cohort of 40 children. These proteins primarily participate in immune activation, the complement pathway, oxygen transport, and reactive oxygen metabolism. Notably, cathepsin Z exhibited a positive correlation with the obstructive apnea hypopnea index, whereas sex hormone-binding globulin (SHBG) was negatively correlated. These proteins were then validated by ELISA in an independent cohort (n=21). Circulating cathepsin Z and SHBG levels displayed acceptable diagnostic performance of OSA with AUC values of 0.863 and 0.738, respectively.

Conclusions

We identified two promising circulating proteins as novel biomarkers for clinical diagnosis and assessment of pediatric OSA severity. Furthermore, the comprehensive proteomic profile in pediatric OSA should aid in exploring the underlying pathophysiological mechanisms associated with this prevalent condition.

Keywords:
Obstructive sleep apnea
Biomarkers
Proteomics
Data-independent acquisition
Abbreviations:
ArI
ArI-resp
BMI
COMP
DDR1
DIA
EPHB3
FLG2
GO
GNPTG
IGHG3
IGHG4
LG3BP
MS
N1%, N2%, N3% and R%
OAHI
ODI
OSA
PSG
ROBO3
ROS
SE
SOD
SpO2
SHBG
T90
tPA
UBE2V1
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