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Excerpts from Clinical Proteomics: New Promises for Early Cancer Detection
by Sara M. Mariani, M.D., Ph.D.

Proteomics, the science that studies the global patterns of protein expression in individual cells, tissues, or body fluids, has been, until recently, a field familiar only to a few initiated in the art. However, as more studies are yielding new data with far-reaching implications, clinicians are starting to look at proteomics as a new source of clues to help in the early diagnosis of cancer and in prediction of clinical outcomes.

Instead of tracking a single biomarker, usually a tumor-associated antigen whose expression is related to a well-defined cancer (ie, prostate-specific antigen [PSA]), proteomics is attempting to define global patterns of protein expression with diagnostic or prognostic value for a particular form of cancer. Such data sets are obtained using large numbers of samples from patients divided in appropriate categories vs healthy controls or patients with good prognosis, analyzed for correlation and significance, and further validated using out-of-sample clinical data.

These new avenues of investigation have been made possible by significant advances in the technologies used in the analysis of complex protein mixtures from very large numbers of samples. High-resolution mass spectroscopy (surface-enhanced laser desorption and ionization time-of-flight mass spectroscopy [SELDI-TOF]), for example, is one of these techniques. The proteomic signatures thus obtained are then correlated with known biologic characteristics and clinical features of the malignancy under study, with diagnostic and prognostic intents.

Whether obtained by direct tumor tissue analysis or resolution of complex protein mixes in body fluids (serum and urine), new protein expression profiles with unique characteristics are indeed being reported with increasing frequency. Identification of the proteins involved, further validation of the complex algorithms used to train analysis of the data, with larger numbers of samples, and verification of the reproducibility of the results obtained are expected to be the next steps in obtaining new screening tools for the diagnosis of cancer and prediction of susceptibility to a number of other malignancies.

The sophistication of the techniques used to set up and run these protein microchip platforms and high-resolution mass spectrometry, as well as the automation processes necessary to achieve large outputs, will probably restrict these diagnostic tests to well-equipped and experienced laboratories. However, high throughput in these centralized facilities is expected, at the same time, to ensure the high level of performance needed and a high index of reproducibility in the results obtained.

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Excerpted with the kind permission of Medscape from WebMD from the conference report, "Clinical Proteomics: New Promises for Early Cancer Detection," which highlights key findings from the 2003 Annual Meeting of the American Association for Cancer Research (April 5-9, 2003; Toronto, Ontario, Canada). Click on the link for access to the full text of this article.

Sara M. Mariani, M.D., Ph.D. is the Deputy Editor of Medscape General Medicine and the Site Editor/Program Director of Medscape Molecular Medicine.




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