Urinary Proteomics Pilot Study for Biomarker Discovery and Diagnosis in Heart Failure with Reduced Ejection Fraction

Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF) may emerge from recent advances in high-throughput urinary proteomics. This could lead to improved diagnosis, risk stratification and management of HFrEF. Urine samples were analyzed...

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Published inPloS one Vol. 11; no. 6; p. e0157167
Main Authors Rossing, Kasper, Bosselmann, Helle Skovmand, Gustafsson, Finn, Zhang, Zhen-Yu, Gu, Yu-Mei, Kuznetsova, Tatiana, Nkuipou-Kenfack, Esther, Mischak, Harald, Staessen, Jan A, Koeck, Thomas, Schou, Morten
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 01.06.2016
Public Library of Science (PLoS)
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Summary:Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF) may emerge from recent advances in high-throughput urinary proteomics. This could lead to improved diagnosis, risk stratification and management of HFrEF. Urine samples were analyzed by on-line capillary electrophoresis coupled to electrospray ionization micro time-of-flight mass spectrometry (CE-MS) to generate individual urinary proteome profiles. In an initial biomarker discovery cohort, analysis of urinary proteome profiles from 33 HFrEF patients and 29 age- and sex-matched individuals without HFrEF resulted in identification of 103 peptides that were significantly differentially excreted in HFrEF. These 103 peptides were used to establish the support vector machine-based HFrEF classifier HFrEF103. In a subsequent validation cohort, HFrEF103 very accurately (area under the curve, AUC = 0.972) discriminated between HFrEF patients (N = 94, sensitivity = 93.6%) and control individuals with and without impaired renal function and hypertension (N = 552, specificity = 92.9%). Interestingly, HFrEF103 showed low sensitivity (12.6%) in individuals with diastolic left ventricular dysfunction (N = 176). The HFrEF-related peptide biomarkers mainly included fragments of fibrillar type I and III collagen but also, e.g., of fibrinogen beta and alpha-1-antitrypsin. CE-MS based urine proteome analysis served as a sensitive tool to determine a vast array of HFrEF-related urinary peptide biomarkers which might help improving our understanding and diagnosis of heart failure.
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Competing Interests: T. Koeck and Esther Nkuipou-Kenfack are employed by Mosaiques-Diagnostics GmbH and H. Mischak is the CEO of Mosaiques- Diagnostics GmbH. Being employed by Mosaiques Diagnostics GmbH did not influence study design, decision to publish or preparation of the manuscript. Urinary proteomic data collection and analysis was performed at Mosaiques Diagnostics GmbH following established standard operating procedures. None of the other authors declared a conflict of interest.
Conceived and designed the experiments: KR HB FG MS JS HM T. Koeck. Performed the experiments: KR HB FG MS JS ZYZ YMG T. Koeck MS ENK. Analyzed the data: KR MS FG HM T. Koeck ENK T. Kuznetsova. Contributed reagents/materials/analysis tools: KR HB FG MS JS ZYZ YMG T. Koeck MS T. Kuznetsova HM. Wrote the paper: KR T. Koeck MS.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0157167