Toxicoproteomics: serum proteomic pattern diagnostics for early detection of drug induced cardiac toxicities and cardioprotection.
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.
Petricoin
Emanuel F
EF
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
Rajapaske
Vinodh
V
Herman
Eugene H
EH
Arekani
Ali M
AM
Ross
Sally
S
Johann
Donald
D
Knapton
Alan
A
Zhang
J
J
Hitt
Ben A
BA
Conrads
Thomas P
TP
Veenstra
Timothy D
TD
Liotta
Lance A
LA
Sistare
Frank D
FD
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
D018943:Anthracyclines; D000880:Anthraquinones; D001798:Blood Proteins