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Validation of serum biomarkers derived from proteomic analysis for the early screening of preeclampsia.

ABSTRACT: To examine the potential value of previously identified biomarkers using proteomics in early screening for preeclampsia (PE).24 blood samples from women who subsequently developed PE and 48 from uncomplicated pregnancies were obtained at 11-13 weeks and analysed after delivery. Cystatin-C, sVCAM-1, and Pappalysin-1 were quantified by ELISA. Maternal characteristics and medical history were recorded.Median values of Cystatin-C, sVCAM-1, and Pappalysin-1 in the PE group as compared to controls were 909.1?gEq/mL versus 480.0?gEq/mL, P = .000, 832.0?gEq/mL versus 738.8?gEq/mL, P = .024, and 234.4?gEq/mL versus 74.9?gEq/mL, P = .064, respectively. Areas under the receiver-operating characteristic curves (AUC, standard error (SE)) for predicting PE were Cystatin-C: 0.90 (SE 0.04), VCAM-1: 0.66 (SE 0.074), and Pappalysin-1: 0.63 (SE 0.083). To discriminate between cases at risk for PE and normal controls, cut-off values of 546.8?gEq/mL for Cystatin-C, 1059.5?gEq/mL for sVCAM-1, and 220.8?gEq/mL for Pappalysin-1 were chosen, providing sensitivity of 91%, 41%, and 54% and specificity of 85%, 100%, and 95%, respectively.sVCAM-1 and Pappalysin-1 do not improve early screening for PE. Cystatin-C, however, seems to be associated with subsequent PE development, but larger studies are necessary to validate these findings.

SUBMITTER: Kolialexi A

PROVIDER: S-EPMC4299787 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Validation of serum biomarkers derived from proteomic analysis for the early screening of preeclampsia.

Kolialexi Aggeliki A Gourgiotis Dimitrios D Daskalakis George G Marmarinos Antonis A Lykoudi Alexandra A Mavreli Danai D Mavrou Ariadni A Papantoniou Nikolas N

Disease markers 20150105

<h4>Aim</h4>To examine the potential value of previously identified biomarkers using proteomics in early screening for preeclampsia (PE).<h4>Methods</h4>24 blood samples from women who subsequently developed PE and 48 from uncomplicated pregnancies were obtained at 11-13 weeks and analysed after delivery. Cystatin-C, sVCAM-1, and Pappalysin-1 were quantified by ELISA. Maternal characteristics and medical history were recorded.<h4>Results</h4>Median values of Cystatin-C, sVCAM-1, and Pappalysin-1 ...[more]

PMID: 25628472

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Project description:BackgroundWe sought to discover serum biomarkers of ankylosing spondylitis (AS) for diagnosis and monitoring disease activity.MethodsWe studied biologic-treatment-naïve AS and healthy control (HC) patients' sera. Eighty samples matched by age, gender, and race (1:1:1 ratio) for AS patients with active disease, inactive disease, and HC were analyzed with SOMAscan™, an aptamer-based discovery platform. T-tests tests were performed for high/low-disease activity AS patients versus HCs (diagnosis) and high versus low disease activity (Monitoring) in a 2:1 and 1:1 ratio, respectively, to identify differentially expressed proteins (DEPs). We used the Cytoscape Molecular Complex Detection (MCODE) plugin to find clusters in protein-protein interaction networks and Ingenuity Pathway Analysis (IPA) for upstream regulators. Lasso regression analysis was performed for diagnosis.ResultsOf the 1317 proteins detected in our diagnosis and monitoring analyses, 367 and 167 (317 and 59, FDR-corrected q < .05) DEPs, respectively, were detected. MCODE identified complement, IL-10 signaling, and immune/interleukin signaling as the top 3 diagnosis PPI clusters. Complement, extracellular matrix organization/proteoglycans, and MAPK/RAS signaling were the top 3 monitoring PPI clusters. IPA showed interleukin 23/17 (interleukin 22, interleukin 23A), TNF (TNF receptor-associated factor 3), cGAS-STING (cyclic GMP-AMP synthase, Stimulator of Interferon Gene 1), and Jak/Stat (Signal transducer and activator of transcription 1), signaling in predicted upstream regulators. Lasso regression identified a Diagnostic 13-protein model predictive of AS. This model had a sensitivity of 0.75, specificity of 0.90, a kappa of 0.59, and overall accuracy of 0.80 (95% CI: 0.61-0.92). The AS vs HC ROC curve was 0.79 (95% CI: 0.61-0.96).ConclusionWe identified multiple candidate AS diagnostic and disease activity monitoring serum biomarkers using a comprehensive proteomic screen. Enrichment analysis identified key pathways in AS diagnosis and monitoring. Lasso regression identified a multi-protein panel with modest predictive ability.

Project description:BACKGROUND:Placental protein expression plays a crucial role during pregnancy. We hypothesized that: (1) circulating levels of pregnancy-associated, placenta-related proteins throughout gestation reflect the temporal progression of the uncomplicated, full-term pregnancy, and can effectively estimate gestational ages (GAs); and (2) preeclampsia (PE) is associated with disruptions in these protein levels early in gestation; and can identify impending PE. We also compared gestational profiles of proteins in the human and mouse, using pregnant heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like symptoms. METHODS:Serum levels of placenta-related proteins-leptin (LEP), chorionic somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)-were quantified by ELISA in blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 20 subjects who developed PE with 61 samples). Multivariate analysis was performed to estimate the GA in normal pregnancy. Mean-squared errors of GA estimations were used to identify impending PE. The human protein profiles were then compared with those in the pregnant HO-1 Het mice. RESULTS:An elastic net-based gestational dating model was developed (R2 = 0.76) and validated (R2 = 0.61) using serum levels of the 6 proteins measured at various GAs from women with normal uncomplicated pregnancies. In women who developed PE, the model was not (R2 = -0.17) associated with GA. Deviations from the model estimations were observed in women who developed PE (P = 0.01). The model developed with 5 proteins (ELA excluded) performed similarly from sera from normal human (R2 = 0.68) and WT mouse (R2 = 0.85) pregnancies. Disruptions of this model were observed in both human PE-associated (R2 = 0.27) and mouse HO-1 Het (R2 = 0.30) pregnancies. LEP outperformed sFlt-1 and PlGF in differentiating impending PE at early human and late mouse GAs. CONCLUSIONS:Serum placenta-related protein profiles are temporally regulated throughout normal pregnancies and significantly disrupted in women who develop PE. LEP changes earlier than the well-established biomarkers (sFlt-1 and PlGF). There may be evidence of a causative action of HO-1 deficiency in LEP upregulation in a PE-like murine model.

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Validation of serum biomarkers derived from proteomic analysis for the early screening of preeclampsia.

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Validation of serum biomarkers derived from proteomic analysis for the early screening of preeclampsia.

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