4.6 Article

Serum Proteomic Analysis by Tandem Mass Tag-Based Quantitative Proteomics in Pediatric Obstructive Sleep Apnea

Journal

FRONTIERS IN MOLECULAR BIOSCIENCES
Volume 9, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2022.762336

Keywords

obstructive sleep apnea; proteomic analysis; tandem mass tags; differentially expressed proteins; serum; experimental validation

Funding

  1. Shenzhen Science and Technology Program [JCYJ20210324113612032, JCYJ20210324142207019]
  2. National Natural Science Foundation of China [82004046]
  3. Guangdong Basic and Applied Basic Research Foundation [2020A1515010592]
  4. Shenzhen Key Medical Discipline Construction Fund [SZXK039]
  5. Science and Technology Development Special Fund of Shenzhen Longgang District [LGKCYLWS2020087, LGKCYLWS2019000864]
  6. Shenzhen Peoples Hospital Clinical Research Project [SYLCYJ202001]
  7. Special Funds for Economic Development of Guangming District [2020R10176]

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In this study, differentially expressed proteins in the serum of pediatric obstructive sleep apnea (OSA) patients were identified using tandem mass tag (TMT)-based proteomic analysis. The results suggested that several signaling pathways may be associated with the pathophysiology of OSA, and experimental validation studies revealed potential key proteins involved in OSA.
Pediatric obstructive sleep apnea (OSA) is a frequent respiratory disorder with an estimated prevalence of 3-6% in the general population. However, the underlying pathophysiology of OSA remains unclear. Recently, proteomic analysis using high-resolution and high-throughput mass spectrometry has been widely used in the field of medical sciences. In the present study, tandem mass tag (TMT)-based proteomic analysis was performed in the serum of patients with OSA. The proteomic analysis revealed a set of differentially expressed proteins that may be associated with the pathophysiology of OSA. The differentially expressed proteins in patients with OSA were enriched in pathways including phagosome and glycan synthesis/degradation, immune response, and the hedgehog signaling pathway, indicating that such functions are key targets of OSA. Moreover, the experimental validation studies revealed that four proteins including ANTXR1, COLEC10, NCAM1, and VNN1 were reduced in the serum from patients with moderate and severe OSA, while MAN1A1 and CSPG4 protein levels were elevated in the serum from patients with severe OSA. The protein levels of ANTXR1, COLEC10, NCAM1, and VNN1 were inversely correlated with apnea-hypopnea index (AHI) in the recruited subjects, while the protein level of MAN1A1 was positively correlated with AHI, and no significant correlation was detected between CSPG4 protein and AHI. In summary, the present study for the first time identified differentially expressed proteins in the serum from OSA patients with different severities by using TMT-based proteomic analysis. The functional enrichment studies suggested that several signaling pathways may be associated with the pathophysiology of OSA. The experimental validation results indicated that six proteins including ANTXR1, COLEC10, NCAM1, VNN1, CGPG4, and MAN1A1 may play important roles in the pathophysiology of OSA, which requires further mechanistic investigation.

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