Abstract: ObjectiveTo detect differentially expressed proteins related with ventricular septal defect(VSD) by utilizing isobaric tags for relative and absolute quantitation(iTRAQ) labeling coupled with liquid chromatography and matrix-assisted laser desorption ionization tandem time of flight mass spectrometry(LC-MALDI-TOF/TOF MS) technology for the screening of potential serum protein biomarkers of VSD and to explore the pathogenesis of VSD. MethodsThe serum samples were collected from 20 children with VSD,20 healthy children and 20 children with atrial septal defect(ASD) matched to the VSD cases in age,gender and race.Multiple affinity removal system(MARS) was adopted to exclude 14 kinds of high abundant proteins in the serum.Proteins differentially expressed in the serum of patients with VSD were identified with iTRAQ labeling coupled with LC-MALDI-TOF/TOF MS technology and analysed with bioinformatics tools and methods. ResultsA total of 329 proteins with the confidence coefficient above 95% were recognised,in which 36 differentially expressed proteins related with VSD,including secreted protein acidic rich in cysteine (SPARC) and adiponection,were identified.For the 38 proteins,21 proteins were over-expressed(>1.2 fold) and 15 proteins were under-expressed(<0.83 fold) in VSD group compared with those in both healthy group and ASD group. ConclusionA serial of differentially expressed proteins associated with VSD were identified in this pilot study.The results suggest that iTRAQ labeling combined with LC-MALDI-TOF/TOF MS technology is a feasible strategy for the screening of potential serum protein biomarkers of VSD and the study of VSD pathogenesis.