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[email protected] 456 JournalofProteom e Research •Vol. 2, No. 5, 2003
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[email protected] 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.
W
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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