Novel Protein Biomarkers of Monoamine Metabolism Defects Correlate with Disease Severity

2020 ◽  
Author(s):  
Alba Tristán‐Noguero ◽  
Eva Borràs ◽  
Marta Molero‐Luis ◽  
Tessa Wassenberg ◽  
Tessa Peters ◽  
...  
Keyword(s):  
Disease Severity ◽  
Protein Biomarkers ◽  
Monoamine Metabolism ◽  
Novel Protein

Abstract 14727: Meteorin-like Glial Cell Differentiation Regulator is a Novel Protein Biomarker of Cardiovascular Outcomes in Patients With Diabetes and Vascular Disease: A TECOS Substudy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Lauren K Truby ◽  
Jessica A Regan ◽  
Maggie Nguyen ◽  
Stephani Giamberardino ◽  
Robert J Mentz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Conditional Logistic Regression ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Specific Protein ◽  
Cardiovascular Outcomes ◽  
Diabetic Patients ◽  
Proteomic Profiling ◽  
Protein Biomarkers ◽  
Novel Protein

Introduction: To date, there are limited data on the potential role of proteomic biomarkers to predict future cardiovascular (CV) events among patients with type 2 diabetes mellitus (DM). Hypothesis: Specific protein biomarkers will be predictive of major adverse CV events (MACE) and incident heart failure hospitalization (HFH) among patients with DM. Methods: Using the Olink aptamer-based platform, we performed proteomic profiling (>700 proteins) on 440 paired cases and matched controls from placebo-assigned participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Cases were defined as having met the primary composite outcome of MACE or incident HFH and matched to controls on baseline prevalent heart failure, coronary artery disease, BMI, hemoglobin A1C, creatinine, low-density lipoprotein cholesterol, fasting status and ejection fraction. Conditional logistic regression was used to determine the association between log-transformed relative protein expression and incident MACE or HFH. False-discovery-rate (FDR) was used to adjust for multiple comparisons. Results: We identified three specific proteins that were significantly associated with prevalent MACE or HFH: METRNL, Notch 3, and ROR1 (OR 2.1, 1.6, 1.7 and q-value 0.01, 0.02, and 0.05 respectively) (Figure 1). METRNL, in particular, performed similarly to the established biomarker NT-proBNP (Figure 1). When MACE and HFH were analyzed separately, METRNL, in particular, remained strongly associated with both outcomes (OR 2.0, p<0.001 and OR 2.7, p=0.05). Conclusions: Three novel protein biomarkers, in particular METRNL (a circulating adipokine that regulates insulin-sensitivity), may identify diabetic patients at high risk for subsequent HF and MACE. Additional studies are needed to replicate these findings and uncover the biologic mechanism linking adipokine signaling and heart failure.

FRI0576 IDENTIFICATION OF SERUM PROTEIN BIOMARKERS ASSOCIATED WITH RA DISEASE SEVERITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 891-892
Author(s):  
D. Galbraith ◽  
M. Caliskan ◽  
O. Jabado ◽  
S. Hu ◽  
R. Fleischmann ◽  
...  
Keyword(s):  
Disease Severity ◽  
Serum Protein ◽  
Dynamic Range ◽  
Serum Proteins ◽  
Differentially Expressed ◽  
Protein Abundance ◽  
Healthy Individuals ◽  
Protein Biomarkers ◽  
Research Support ◽  
Baseline Serum

Background:RA is a systemic autoimmune disease with heterogeneous manifestation. Recent advances in serum proteomics, such as the SomaScan®platform (SomaLogic, Inc., Boulder, USA), allow for a deeper exploration of the protein biomarkers associated with RA and a better understanding of the molecular aetiology of the disease.Objectives:To characterise the differences in baseline serum proteome of patients with RA (enrolled in the Phase IIIb Abatacept vs adaliMumab comParison in bioLogic-naïvERA subjects with background MTX [AMPLE] study)1compared with a healthy population, and to identify serum protein biomarkers associated with disease severity and radiographic progression.Methods:Patients in the AMPLE study had an inadequate response to MTX and were naïve to biologic DMARDs. Protein abundance was assessed in baseline serum samples from 440 AMPLE study patients and 123 healthy individuals with matching demographics using the SomaScan®platform, with 5000+ slow off-rate modified aptamers and up to 8 log of dynamic range.2Differential abundance testing was performed using linear models to identify differences in protein abundance in patients with RA vs healthy individuals. A separate analysis using a linear model was conducted in only the patients with RA to identify the proteins associated with DAS28 (CRP) and TSS. Pathway analyses were performed for proteins significantly (false discovery rate-adjusted p value <0.05) associated with RA and the disease severity measurements to identify over-representation of the molecular pathways.Results:Compared with healthy individuals, >2000 serum proteins were significantly differentially expressed in patients with RA, including many proteins that have been associated with RA (e.g. serum amyloid A [SAA], CRP) and complement. Most of the protein expression differences were of small magnitude (fold change <2). Proteins that were differentially expressed between patients with RA and healthy individuals were enriched in interleukin signalling, neutrophil degranulation, platelet activation/degranulation and extracellular matrix organisation pathways. DAS28 (CRP) was significantly associated with several biomarkers, including SAA, fibrinogen and CRP; in general, proteins associated with DAS28 (CRP) were most strongly enriched in the platelet activation/degranulation pathways (Figure 1), also seen in patients with RA vs healthy individuals. Additionally, many proteins were significantly associated with TSS, including SAA, matrix metalloproteinase-3 and cartilage acidic protein 1. Here, the proteins were most strongly enriched in the extracellular matrix remodelling pathways (Figure 2).Conclusion:Our study revealed that thousands of serum proteins are differentially expressed and several pathways are dysregulated between patients with RA and healthy individuals. Additional pathways were identified that reflect disease severity, including joint damage, distinct from those pathways associated with the disease. The SomaScan®platform provides a unique proteomic tool with a wide dynamic range for the identification of serum protein biomarkers associated with RA and disease severity. Proteomic signatures should be considered in clinical trials to better understand disease pathogenesis and predict risk in response to treatment.References:[1]Schiff M, et al.Ann Rheum Dis2014;73:86–94.[2]Gold L, et al.PLoS One2010;5:e15004.Acknowledgments:Rachel Rankin (medical writing, Caudex; funding: Bristol-Myers Squibb)Disclosure of Interests:David Galbraith Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Minal Caliskan Employee of: Bristol-Myers Squibb, Omar Jabado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sarah Hu Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Michael Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo, Lily, Sanofi/Regeneron, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Crescendo, Gilead, Horizon, Lily, Pfizer, Roche, Sean Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Michael A Maldonado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Sheng Gao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb

scholarly journals Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau

2020 ◽  
Vol 46 (1) ◽  
pp. 98-115 ◽  
Author(s):  
Sruti Rayaprolu ◽  
Lenora Higginbotham ◽  
Pritha Bagchi ◽  
Caroline M. Watson ◽  
Tian Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Network ◽  
Protein Biomarkers ◽  
Cellular Processes ◽  
Complex Protein ◽  
Underlying Mechanisms ◽  
Novel Protein

AbstractThe repeated failures of amyloid-targeting therapies have challenged our narrow understanding of Alzheimer’s disease (AD) pathogenesis and inspired wide-ranging investigations into the underlying mechanisms of disease. Increasing evidence indicates that AD develops from an intricate web of biochemical and cellular processes that extend far beyond amyloid and tau accumulation. This growing recognition surrounding the diversity of AD pathophysiology underscores the need for holistic systems-based approaches to explore AD pathogenesis. Here we describe how network-based proteomics has emerged as a powerful tool and how its application to the AD brain has provided an informative framework for the complex protein pathophysiology underlying the disease. Furthermore, we outline how the AD brain network proteome can be leveraged to advance additional scientific and translational efforts, including the discovery of novel protein biomarkers of disease.

Identification of Novel Protein Biomarkers of Preterm Birth in Human Cervical−Vaginal Fluid

2007 ◽  
Vol 6 (4) ◽  
pp. 1269-1276 ◽  
Author(s):  
Leonardo Pereira ◽  
Ashok P. Reddy ◽  
Thomas Jacob ◽  
Archana Thomas ◽  
Kimberly A. Schneider ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Vaginal Fluid ◽  
Protein Biomarkers ◽  
Novel Protein

scholarly journals Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs

2014 ◽  
Vol 126 (12) ◽  
pp. 857-867 ◽  
Author(s):  
Hui-juan Wang ◽  
Bao-zeng Wang ◽  
Peng-jun Zhang ◽  
Jie Deng ◽  
Zhi-rui Zhao ◽  
...  
Keyword(s):  
Serum Protein ◽  
Sofa Score ◽  
Predictive Value ◽  
Mirna Target ◽  
Target Genes ◽  
Apache Ii Score ◽  
Protein Biomarkers ◽  
Combined Analysis ◽  
Better Than ◽  
Novel Protein

Four novel protein biomarkers encoded by the miRNA target genes were identified for patients with sepsis. The combined analysis of the four proteins indicated that their predictive value for sepsis prognosis was better than the values for the SOFA score and APACHE II score.

scholarly journals Discovery and Validation of Novel Protein Biomarkers in Ovarian Cancer Patient Urine

2018 ◽  
Vol 12 (3) ◽  
pp. 1700135 ◽  
Author(s):  
Jarrod J. Sandow ◽  
Adam Rainczuk ◽  
Giuseppe Infusini ◽  
Ming Makanji ◽  
Maree Bilandzic ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patient ◽  
Ovarian Cancer Patient ◽  
Protein Biomarkers ◽  
Novel Protein

Novel protein biomarkers associated with coronary artery disease in statin-treated patients with familial hypercholesterolemia

2017 ◽  
Vol 11 (3) ◽  
pp. 682-693 ◽  
Author(s):  
Sven Bos ◽  
Michael Phillips ◽  
Gerald F. Watts ◽  
Adrie J.M. Verhoeven ◽  
Eric J.G. Sijbrands ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Protein Biomarkers ◽  
Artery Disease ◽  
Novel Protein
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