What Is New in Proteomics? Biomarkers - ACS Publications

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What Is New in Proteomics? Biomarkers

ASSOCIATE EDITORS

Joshua LaBaer Harvard Medical School

György Marko-Varga AstraZeneca and Lund University

EDITORIAL ADVISORY BOARD

Ruedi H. Aebersold Institute for Systems Biology

Leigh Anderson Plasma Proteome Institute

Ettore Appella National Cancer Institute

Ronald Beavis University of Chicago

Walter Blackstock Cellzome

Brian Chait The Rockefeller University

Patrick L. Coleman 3M

Catherine Fenselau University of Maryland

Daniel Figeys MDS Proteomics

Sam Hanash University of Michigan

Stanley Hefta Bristol-Myers Squibb

Donald F. Hunt University of Virginia

Barry L. Karger Northeastern University

Daniel C. Liebler Vanderbilt University School of Medicine

Lance Liotta National Cancer Institute

Matthias Mann University of Southern Denmark

e’re now fairly certain as to what was the hot topic of the year: none other than the well-worn term biomarkers. Two good questions to pose on observing this phenomenon are “What does the term biomarker exactly mean?” and “What is responsible for its immense popularity?” Suffice it to say, it is difficult to go to a scientific meeting these days without hearing the word used repeatedly in almost all lectures, and now we are observing new meetings that are organized around the term. There is actually a whole genre appearing, so that we have a number of variations, such as bridging biomarker, clinical biomarker, diagnostic biomarker, validated biomarker, and so on. On a simple level, a biomarker should indeed be a meaningful marker of a biological process, and therefore the term’s exact definition would be related to the actual field of use or application. For example, a clinical biomarker should have predictive value (a rarely observed example) or something that can be used for patient segregation or decisions on suitable treatment regimes. In a clinical biomarker study, one would begin with retrospective samples and observe a set of proteins that are associated with a particular disease population. Then, one would study the disappearance of such markers during therapeutic intervention, such as after surgery, radiation, or drug therapy. The marker would be expected to reappear on recurrence of the disease. After this preliminary validation process, the marker would be used in a prospective study to see if the panel of proteins has predictive value. At this point, most markers fail. The prospective study test sample is important if one wishes to have a widely used diagnostic. To date, tissue samples have not resulted in anything but research tests or one-off (individual) patient studies. For general use, a plasma or serum diagnostic must be developed. This is a much greater challenge because a tissue sample generally has a smaller dynamic range than plasma and contains much higher levels of a particular tumor antigen. At a late stage in the disease, one would anticipate greater concentrations of the biomarker in plasma because of processes such as cell death or secretion. However, the detection problem arises with early detection when very low levels of the disease marker may be present, making the blood test not useful. We therefore have the challenge for proteomics researchers to develop a proteomic analysis of sufficient sensitivity to allow the early detection of disease biomarkers. Similar improvements in technology will be required to apply biomarkers in other fields as well; for example, the application of proteomics to toxicology poses similar technical and adoption challenges.

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Stephen A. Martin Applied Biosystems

Jeremy Nicholson Imperial College of London

Emanuel Petricoin Food and Drug Administration

J. Michael Ramsey Oak Ridge National Laboratory

Pier Giorgio Righetti University of Verona

John T. Stults Biospect

Peter Wagner Zyomyx

Keith Williams Proteome Systems

Qi-Chang Xia Shanghai Institute of Biochemistry

John R.Yates, III The Scripps Research Institute

© 2003 American Chemical Society

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