Two-dimensional differential in-gel electrophoresis proteomic approaches reveal urine candidate biomarkers in pediatric obstructive sleep apnea.
BACKGROUND
Sleep studies are laborious, expensive, inaccessible, and inconvenient for diagnosing obstructive sleep apnea (OSA) in children.


OBJECTIVE
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.


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.
Section of Pediatric Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, Illinois, USA. dgozal@peds.bsd.uchicago.edu
David
D
Gozal
Saeed
S
Jortani
Ayelet B
AB
Snow
Leila
L
Kheirandish-Gozal
Rakesh
R
Bhattacharjee
Jinkwan
J
Kim
Oscar Sans
OS
Capdevila
D015415:Biomarkers / Q000652:urine; D015153:Blotting, Western; D002648:Child; D015331:Cohort Studies; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D017286:Polysomnography; D011237:Predictive Value of Tests; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020181:Sleep Apnea, Obstructive / Q000652:urine*
D015415:Biomarkers; D020543:Proteome