title: Urinary proteomics to support diagnosis of stroke.
abstract: Accurate diagnosis in suspected ischaemic stroke can be difficult. We explored the urinary proteome in patients with stroke (n = 69), compared to controls (n = 33), and developed a biomarker model for the diagnosis of stroke. We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry. Potentially disease-specific peptides were identified and a classifier based on these was generated using support vector machine-based software. Candidate biomarkers were sequenced by liquid chromatography-tandem mass spectrometry. We developed two biomarker-based classifiers, employing 14 biomarkers (nominal p-value <0.004) or 35 biomarkers (nominal p-value <0.01). When tested on a blinded test set of 47 independent samples, the classification factor was significantly different between groups; for the 35 biomarker model, median value of the classifier was 0.49 (-0.30 to 1.25) in cases compared to -1.04 (IQR -1.86 to -0.09) in controls, p<0.001. The 35 biomarker classifier gave sensitivity of 56%, specificity was 93% and the AUC on ROC analysis was 0.86. This study supports the potential for urinary proteomic biomarker models to assist with the diagnosis of acute stroke in those with mild symptoms. We now plan to refine further and explore the clinical utility of such a test in large prospective clinical trials.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medicine, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom. jesse.dawson@glasgow.ac.uk
authors.forename: Jesse
authors.initials: J
authors.lastname: Dawson
authors.forename: Matthew
authors.initials: M
authors.lastname: Walters
authors.forename: Christian
authors.initials: C
authors.lastname: Delles
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.forename: William
authors.initials: W
authors.lastname: Mullen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D015415:Biomarkers / Q000737:chemistry / Q000652:urine; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D011507:Proteinuria / Q000652:urine*; D040901:Proteomics; D020521:Stroke / Q000175:diagnosis* / Q000652:urine
chemical_list: D015415:Biomarkers