Identification of urinary biomarkers for the prediction of gestational diabetes mellitus in early second trimester of young gravidae based on iTRAQ quantitative proteomics

Abstract

Gestational Diabetes Mellitus (GDM) has brought great harm to maternal and fetus. Up to now, only a few plasma biomarkers for its early diagnosis have been reported; nevertheless, there is no report about identification of urinary biomarkers for prediction of GDM. Thus, it is necessary to correct this deficiency. In our study, urine samples were collected from 889 healthy young gravidae at the early second trimester (15 to 20 weeks), 69 of whom were subsequently diagnosed with GDM at 24 to 28 weeks. iTRAQ (the isobaric tags for relative and absolute quantification) quantitative proteomics was conducted on sixteen GDM (trial group) and an equal number of matched healthy young gravidae (control group). Validation was performed in 40 cases of each group by ELISA. A total of 1,901 proteins were identified in this study, including 119 significantly differential proteins (fold change ≧1.2 or ≦0.83 and p < 0.05). Compared with control group, 83 differential proteins were increased and 36 proteins were decreased in GDM group. The validation for expression of CD59 and IL1RA showed significant difference and the area under the receiver operating characteristic curve was 0.729 and 0.899, respectively (p < 0.05). The two candidate protein biomarkers (CD59 and IL1RA) in urine could be an early, noninvasive diagnostic predictors of young pravidae with GDM, and IL1RA is stronger diagnostic power than CD59.

Controversies in Screening and Diagnostic Criteria for Gestational Diabetes in Early and Late Pregnancy

“…A specific protein or metabolite pattern will help to decipher biological processes in a more holistic way. These metabolic “fingerprints” of different body fluid sources could then be used for predictive purposes as has already been demonstrated in small case-control studies ( 48 , 63 ).…”

Testing the Surface Fixation Method in Gestational Diabetes Mellitus

“…Urine samples from patients with GDM have been studied in several ways, for example, the group of Guo et al using iTRAQ (the isobaric tags for relative and absolute quantification) for quantitative proteomics found 83 differential proteins increased and 36 proteins decreased in GDM. They concluded that the two candidate protein biomarkers (CD59 and IL1RA) in urine could be early, noninvasive diagnostic predictors of GDM 17 . More recently, López-Hernández et al analyzed the urinary metabolome profile of GDM patients in the 3rd trimester of pregnancy based on liquid chromatography mass spectrometry, and identified 14 metabolites that were significantly up-regulated in the urine of GDM patients 18 .…”

A Critical Review of Proteomic Studies in Gestational Diabetes Mellitus

“…Moreover, there is also a growing trend for seeking noninvasive testing strategies nowadays. Hence, one study used urine samples to identify biomarkers that could predict GDM [38].…”

“…In addition to clinical validation or functional verification, eight studies also performed expression verification experiments using immunodepletion, western blot, immunohistochemistry, real-time polymerase chain reaction, or bioinformatics database (the Human Protein Atlas) [55] to verify the existence, localization, and change trend of DE proteins. Table 1, five studies evaluated the diagnostic efficiency of a selected list of significantly changed proteins [31,37,38,42,47]. The concentrations of target proteins were measured by the ELISA or MRM method in serum, plasma, or urine samples.…”