title: The use of multiplexed MRM for the discovery of biomarkers to differentiate iron-deficiency anemia from anemia of inflammation.
abstract: In this study we demonstrate the use of a multiplexed MRM-based assay to distinguish among normal (NL) and iron-metabolism disorder mouse models, particularly, iron-deficiency anemia (IDA), inflammation (INFL), and inflammation and anemia (INFL+IDA). Our initial panel of potential biomarkers was based on the analysis of 14 proteins expressed by candidate genes involved in iron transport and metabolism. Based on this study, we were able to identify a panel of 8 biomarker proteins: apolipoprotein A4 (APO4), transferrin, transferrin receptor 1, ceruloplasmin, haptoglobin, lactoferrin, hemopexin, and matrix metalloproteinase-8 (MMP8) that clearly distinguish among the normal and disease models. Within this set of proteins, transferrin showed the best individual classification accuracy over all samples (72%) and within the NL group (94%). Compared to the best single-protein biomarker, transferrin, the use of the composite 8-protein biomarker panel improved the classification accuracy from 94% to 100% in the NL group, from 50% to 72% in the INFL group, from 66% to 96% in the IDA group, and from 79% to 83% in the INFL+IDA group. Based on these findings, validation of the utility of this potentially important biomarker panel in human samples in an effort to differentiate IDA, inflammation, and combinations thereof, is now warranted. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.
authors.affiliation: University of Victoria - Genome British Columbia Proteomics Centre, University of Victoria, #3101-4464 Markham Street, Vancouver Island Technology Park Victoria, Canada BC V8Z7X8.
authors.forename: Dominik
authors.initials: D
authors.lastname: Domanski
authors.forename: Gabriela V
authors.initials: GV
authors.lastname: Cohen Freue
authors.forename: Luis
authors.initials: L
authors.lastname: Sojo
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kuzyk
authors.forename: Leslie
authors.initials: L
authors.lastname: Ratkay
authors.forename: Carol E
authors.initials: CE
authors.lastname: Parker
authors.forename: Y Paul
authors.initials: YP
authors.lastname: Goldberg
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Borchers
mesh_terms: D000740:Anemia / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology; D018798:Anemia, Iron-Deficiency / Q000097:blood* / Q000175:diagnosis*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis* / Q000737:chemistry; D003937:Diagnosis, Differential; D005260:Female; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D010449:Peptide Mapping / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D001798:Blood Proteins