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Two-Dimensional Differential In-Gel Electrophoresis Proteomic Approaches Reveal Urine Candidate Biomarkers in Pediatric Obstructive Sleep Apnea

¹ Section of Pediatric Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, Illinois; and ² Department of Pathology and Laboratory Medicine and ³ Division of Sleep Medicine and Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, Kentucky

Correspondence and requests for reprints should be addressed to David Gozal, M.D., Department of Pediatrics, Comer Children's Hospital, University of Chicago, 5721 S. Maryland Avenue, MC 8000, Suite K-160, Chicago, IL 60637. E-mail: dgozal{at}peds.bsd.uchicago.edu

Rationale: Sleep studies are laborious, expensive, inaccessible, and inconvenient for diagnosing obstructive sleep apnea (OSA) in children.

Objectives: To examine whether the urinary proteome uncovers specific clusters that are differentially expressed in the urine of children with OSA.

Methods: Two-dimensional differential in-gel electrophoresis (2D-DIGE) and mass spectrometry proteomics followed by validation with western blot of ELISA.

Measurements and Main Results: Morning urine proteins from 60 children with polysomnographically confirmed OSA and from matched children with primary snoring (n = 30) and control subjects (n = 30) were assessed. A total of 16 proteins that are differentially expressed in OSA were identified, and 7 were confirmed by either immunoblots or ELISA. Among the latter, receiver–operator curve analyses of urinary concentrations of uromodulin, urocortin-3, orosomucoid-1, and kallikrein assigned favorable predictive properties to these proteins. Furthermore, combinatorial approaches indicated that the presence of values beyond the calculated cutoff concentrations for three or more of the proteins yielded a sensitivity of 95% and a specificity of 100%.

Conclusions: Proteomic approaches reveal that pediatric OSA is associated with specific and consistent alterations in urinary concentrations of specific protein clusters. Future studies aiming to validate this approach as a screening method of habitually snoring children appears warranted.

Key Words: sleep apnea • biomarkers • children • urine

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Sleep studies are laborious, expensive, relatively inaccessible, and inconvenient for diagnosing obstructive sleep apnea (OSA) in children. Proteomic analyses may uncover specific protein clusters that are differentially expressed in the urine of children with OSA. What This Study Adds to the Field Morning urine samples from children fulfilling the polysomnographic and clinical criteria of OSA reveal selective and consistent alterations in specific components of the urinary proteome when compared with children who habitually snore or healthy nonsnoring control children.

 

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