Dataset Information

Validation of a Novel Modified Aptamer-Based Array Proteomic Platform in Patients with End-Stage Renal Disease.

ABSTRACT: End stage renal disease (ESRD) is characterized by complex metabolic abnormalities, yet the clinical relevance of specific biomarkers remains unclear. The development of multiplex diagnostic platforms is creating opportunities to develop novel diagnostic and therapeutic approaches. SOMAscan is an innovative multiplex proteomic platform which can measure >1300 proteins. In the present study, we performed SOMAscan analysis of plasma samples and validated the measurements by comparison with selected biomarkers. We compared concentrations of SOMAscan-measured prostate specific antigen (PSA) between males and females, and validated SOMAscan concentrations of fibroblast growth factor 23 (FGF23), FGF receptor 1 (FGFR1), and FGFR4 using Enzyme-Linked immunosorbent assay (ELISA). The median (25th and 75th percentile) SOMAscan PSA level in males and females was 4304.7 (1815.4 to 7259.5) and 547.8 (521.8 to 993.4) relative fluorescence units (p = 0.002), respectively, suggesting biological plausibility. Pearson correlation between SOMAscan and ELISA was high for FGF23 (R = 0.95, p < 0.001) and FGFR4 (R = 0.69, p < 0.001), indicating significant positive correlation, while a weak correlation was found for FGFR1 (R = 0.13, p = 0.16). In conclusion, there is a good to near-perfect correlation between SOMAscan and standard immunoassays for FGF23 and FGFR4, but not for FGFR1. This technology may be useful to simultaneously measure a large number of plasma proteins in ESRD, and identify clinically important prognostic markers to predict outcomes.

SUBMITTER: Han Z

PROVIDER: S-EPMC6316431 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Validation of a Novel Modified Aptamer-Based Array Proteomic Platform in Patients with End-Stage Renal Disease.

Han Zhongji Z Xiao Zhousheng Z Kalantar-Zadeh Kamyar K Moradi Hamid H Shafi Tariq T Waikar Sushrut S SS Quarles L Darryl LD Yu Zhi Z Tin Adrienne A Coresh Josef J Kovesdy Csaba P CP

Diagnostics (Basel, Switzerland) 20181008 4

End stage renal disease (ESRD) is characterized by complex metabolic abnormalities, yet the clinical relevance of specific biomarkers remains unclear. The development of multiplex diagnostic platforms is creating opportunities to develop novel diagnostic and therapeutic approaches. SOMAscan is an innovative multiplex proteomic platform which can measure >1300 proteins. In the present study, we performed SOMAscan analysis of plasma samples and validated the measurements by comparison with selecte ...[more]

PMID: 30297602

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Project description:BackgroundWe used a large-scale, high-throughput DNA aptamer-based discovery proteomic platform to identify circulating biomarkers of cardiac remodeling and incident heart failure (HF) in community-dwelling individuals.MethodsWe evaluated 1895 FHS (Framingham Heart Study) participants (age 55±10 years, 54% women) who underwent proteomic profiling and echocardiography. Plasma levels of 1305 proteins were related to echocardiographic traits and to incident HF using multivariable regression. Statistically significant protein-HF associations were replicated in the HUNT (Nord-Trøndelag Health) study (n=2497, age 63±10 years, 43% women), and results were meta-analyzed. Genetic variants associated with circulating protein levels (pQTLs) were related to echocardiographic traits in the EchoGen (n=30 201) and to incident HF in the CHARGE (n=20 926) consortia.ResultsSeventeen proteins associated with echocardiographic traits in cross-sectional analyses (false discovery rate <0.10), and 8 of these proteins had pQTLs associated with echocardiographic traits in EchoGen (P<0.0007). In Cox models adjusted for clinical risk factors, 29 proteins demonstrated associations with incident HF in FHS (174 HF events, mean follow-up 19 [limits, 0.2-23.7] years). In meta-analyses of FHS and HUNT, 6 of these proteins were associated with incident HF (P<3.8×10-5; 3 with higher risk: NT-proBNP [N-terminal proB-type natriuretic peptide], TSP2 [thrombospondin-2], MBL [mannose-binding lectin]; and 3 with lower risk: ErbB1 [epidermal growth factor receptor], GDF-11/8 [growth differentiation factor-11/8], and RGMC [hemojuvelin]). For 5 of the 6 proteins, pQTLs were associated with echocardiographic traits (P<0.0006) in EchoGen, and for RGMC, a protein quantitative trait loci was associated with incident HF (P=0.001).ConclusionsA large-scale proteomics approach identified new predictors of cardiac remodeling and incident HF. Future studies are warranted to elucidate how biological pathways represented by these proteins may mediate cardiac remodeling and HF risk and to assess if these proteins can improve HF risk prediction.

Project description:The outbreak of a novel coronavirus (SARS-CoV-2) in 2019 led to a worldwide pandemic, which remains an integral part of our lives to this day. Coronavirus disease (COVID-19) is a flu like condition, often accompanied by high fever and respiratory distress. In some cases, conjointly with other co-morbidities, COVID-19 can become severe, leading to lung arrest and even death. Although well-known from a clinical standpoint, the mechanistic understanding of lethal COVID-19 is still rudimentary. Studying the pathology and changes on a molecular level associated with the resulting COVID-19 disease is impeded by the highly infectious nature of the virus and the concomitant sampling challenges. We were able to procure COVID-19 post-mortem lung tissue specimens by our collaboration with the BSL-3 laboratory of the Biobanking and BioMolecular resources Research Infrastructure Austria which we subjected to state-of-the-art quantitative proteomic analysis to better understand the pulmonary manifestations of lethal COVID-19. Lung tissue samples from age-matched non-COVID-19 patients who died within the same period were used as controls. Samples were subjected to parallel accumulation-serial fragmentation combined with data-independent acquisition (diaPASEF) on a timsTOF Pro and obtained raw data was processed using DIA-NN software. Here we report that terminal COVID-19 patients display an increase in inflammation, acute immune response and blood clot formation (with concomitant triggering of fibrinolysis). Furthermore, we describe that COVID-19 diseased lungs undergo severe extracellular matrix restructuring, which was corroborated on the histopathological level. However, although undergoing an injury, diseased lungs seem to have impaired proliferative and tissue repair signalling, with several key kinase-mediated signalling pathways being less active. This might provide a mechanistic link to post-acute sequelae of COVID-19 (PASC; "Long COVID"). Overall, we emphasize the importance of histopathological patient stratification when interpreting molecular COVID-19 data.

Project description:OBJECTIVE:Serum albumin is a marker of malnutrition and inflammation and has been demonstrated as a strong predictor of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Yet, whether serum albumin levels in late-stage CKD are associated with adverse outcomes after the transition to ESRD is unknown. We hypothesize that lower levels and a decline in serum albumin in late-stage CKD are associated with higher risk of mortality and hospitalization rates 1 year after transition to ESRD. DESIGN AND METHODS:This retrospective cohort study included 29,124 US veterans with advanced CKD transitioning to ESRD between 2007 and 2015. We evaluated the association of pre-ESRD (91 days before transition) serum albumin with 12-month post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates as well as the association of 1-year pre-ESRD albumin slope and 12-month post-ESRD mortality using hierarchical multivariable adjustments. RESULTS:There was a negative linear association between serum albumin and all-cause mortality, such that risk doubled (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.87, 2.28) for patients with the lowest serum albumin <2.8 g/dL (ref: ?4.0 g/dL) after full adjustment. A consistent relationship was observed between serum albumin and cardiovascular and infection-related mortality, and hospitalization outcomes. An increase in serum albumin of >0.25 g/dL/year was associated with reduced mortality risk (HR: 0.76, 95% CI: 0.63, 0.91) compared with a slight decline in albumin (ref: >-0.25 to 0 g/dL/year), whereas a decline more than 0.5 g/dL/year was associated with a 55% higher risk in mortality (HR: 1.55, 95% CI: 1.43, 1.68) in fully adjusted models. CONCLUSIONS:Lower pre-ESRD serum albumin was associated with higher post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates. Declining serum albumin levels in the pre-ESRD period were also associated with worse 12-month post-ESRD mortality.

Dataset Information

Validation of a Novel Modified Aptamer-Based Array Proteomic Platform in Patients with End-Stage Renal Disease.

Publications

Validation of a Novel Modified Aptamer-Based Array Proteomic Platform in Patients with End-Stage Renal Disease.

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