title: Toxicoproteomics: serum proteomic pattern diagnostics for early detection of drug induced cardiac toxicities and cardioprotection.
abstract: Proteomics is more than just generating lists of proteins that increase or decrease in expression as a cause or consequence of pathology. The goal should be to characterize the information flow through the intercellular protein circuitry which communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. The nature of this information can be a cause, or a consequence, of disease and toxicity based processes as cascades of reinforcing information percolate through the system and become reflected in changing proteomic information content of the circulation. Serum Proteomic Pattern Diagnostics is a new type of proteomic platform in which patterns of proteomic signatures from high dimensional mass spectrometry data are used as a diagnostic classifier. While this approach has shown tremendous promise in early detection of cancers, detection of drug-induced toxicity may also be possible with this same technology. Analysis of serum from rat models of anthracycline and anthracenedione induced cardiotoxicity indicate the potential clinical utility of diagnostic proteomic patterns where low molecular weight peptides and protein fragments may have higher accuracy than traditional biomarkers of cardiotoxicity such as troponins. These fragments may one day be harvested by circulating nanoparticles designed to absorb, enrich and amplify the diagnostic biomarker repertoire generated even at the critical initial stages of toxicity.
authors.affiliation: FDA-NCI Clinical Proteomics Program, Office of Cell and Gene Therapies, Center for Biologic Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. petricoin@cber.fda.gov
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: Vinodh
authors.initials: V
authors.lastname: Rajapaske
authors.forename: Eugene H
authors.initials: EH
authors.lastname: Herman
authors.forename: Ali M
authors.initials: AM
authors.lastname: Arekani
authors.forename: Sally
authors.initials: S
authors.lastname: Ross
authors.forename: Donald
authors.initials: D
authors.lastname: Johann
authors.forename: Alan
authors.initials: A
authors.lastname: Knapton
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Ben A
authors.initials: BA
authors.lastname: Hitt
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrads
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Lance A
authors.initials: LA
authors.lastname: Liotta
authors.forename: Frank D
authors.initials: FD
authors.lastname: Sistare
mesh_terms: D000818:Animals; D018943:Anthracyclines / Q000633:toxicity; D000880:Anthraquinones / Q000633:toxicity; D001798:Blood Proteins / Q000032:analysis*; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D013058:Mass Spectrometry; D008954:Models, Biological; D025202:Molecular Diagnostic Techniques / Q000295:instrumentation / Q000379:methods; D036103:Nanotechnology; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D014116:Toxicology
chemical_list: D018943:Anthracyclines; D000880:Anthraquinones; D001798:Blood Proteins