Quantitative Comparative Proteomics Reveals Candidate Biomarkers for the Early Prediction of Gestational Diabetes Mellitus: A Preliminary Study

Abstract

Aim: To identify differentially expressed proteins (DEPs) in 1 st trimester maternal plasma between pregnant women at risk for gestational diabetes mellitus (GDM) and uncomplicated controls. Materials and Methods: Firsttrimester plasma from five women who developed GDM and five from non-diabetic ones were analyzed using isobaric tag for relative and absolute quantitation -labeled proteomics. Enzyme-linked immunosorbent assay was further applied in an independent cohort of 25 GDM cases and 25 controls for verification. Results: Prenylcysteine oxidase 1 (PCYOX1), beta-ala-his dipeptidase (CNDP1), extracellular matrix protein 1 (ECM1), basement membrane-specific heparan sulfate proteoglycan core protein (HSPG2), thrombospondin-4 (TSP-4) demonstrated significant differences in expression between the two groups (p<0.05). DEPs are mainly associated with complement and coagulation cascades. Conclusion: The reported plasma proteomic changes represent potential biomarkers for the early identification of women at risk for GDM. Future studies using larger and more diverse cohorts are necessary to assess the clinical utility of these findings.

Proteome profiling of gestational diabetes mellitus at 16‐18 weeks revealed by LC‐MS/MS

“…Several of the proteins identified in our study have been previously reported by other groups at early GDM biomarkers screening including sex hormone‐binding globulin (SHBG), C‐reactive protein (CRP), serum amyloid P‐component, and fibrinogen alpha chain reported as candidate biomarkers 28,34,35 . Recently, Mavreli et al 18 using proteomic analyses identified overexpression of prenylcysteine oxidase 1 (PCYOX1), beta‐ala‐his dipeptidase (CNDP1), extracellular matrix protein 1 (ECM1), basement membrane‐specific heparan sulfate proteoglycan core protein (HSPG2), and thrombospondin 4 (TSP‐4) in the 1st‐trimester maternal plasma of women who were subsequently diagnosed with GDM followed by confirmatory ELISA.…”

A Critical Review of Proteomic Studies in Gestational Diabetes Mellitus

“…Plasma or serum components can further be extracted from blood to remove cell parts or platelets. Among the ten studies using peripheral blood, five studies used plasma specimens (Figure 1(b)) [27,32,39,44,47], and the remaining studies used serum samples. Moreover, there is also a growing trend for seeking noninvasive testing strategies nowadays.…”

“…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.…”

“…There are generally three periods of sampling time among the reviewed studies ( Figure 1(c) ). First, peripheral blood and urine samples were drawn before diagnosis and used to identify biomarkers for early prediction [ 27 , 32 , 37 , 38 , 42 , 47 ]. Second, peripheral blood and urine exosome samples were also drawn at the same time with diagnosis and used to identify biomarkers for precision diagnosis or classification [ 29 , 31 , 41 , 45 ].…”

“…In recent years, more and more proteomic studies have been performed to construct differential expression profiling or to identify potential biomarkers for GDM and its complications. After an extensive PubMed search for proteomic studies of GDM using mass spectrometry, a total of 21 representative full-length research articles are included in this review [ 27 – 47 ]. The detailed information of the reviewed literatures are listed in Supplementary Data 1.…”