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Proteomic profiles of cancer |
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| Under the general heading of cancer, boundless complex variations exist, which lead to vast differences in the length of survival, effectiveness of treatments, quality of life, and so on.Breaking cancer into categories such as breast cancer and leukemia, or even further dividing these diseases into subsections, such as B-cell chronic lymphocytic leukemia (B-CLL), still gives a highly diverse set of possible outcomes. To explain the underlying nature of this variability, the active proteins must be analyzed and compared across a large number of similarly diagnosed patients presenting an array of clinical manifestations.
Researchers from Austria and Germany have shown that large-scale proteomics analysis is a potential tool for increasing the precision of cancer diagnosis and identifying possible new drug targets. The scientists obtained protein-expression profiles for 24 patients with B-CLL using 2-D gel electrophoresis (Int. J. Cancer 2001, 91, 180–186). The results were combined and correlated to clinical data. A database was createdwith “compartments” for every spot on the gels in which protein was detected. The intensity of each spot and patient identification information were exported to the database, where statistical comparisons were made among patients with different chromosomal characteristics and among those with different survival times. The team found some notable distinctions between populations. Twenty-five proteins showed differencesin their intensities such that the researchers could discriminate between three different chromosome band deletions, important markers of disease progression rate. Furthermore, the intensities of 12 proteins correlated with survival times. Reduced levels of these proteins, which included the enzymes thioredoxin peroxidase 2 and protein disulfide isomerase, were linked to shorter survival times.But the researchers warn that this result does not “necessarily correlate with [the enzymes’] suggested role in drug resistance” and thatadditional studies are required to explain the observation. The promise that this approach offers for cancer classification and drug discovery efforts is clear. There is still much to be accomplished, however, in terms of electrophoresis improvements and developments in data acquisition and analysis, before the protein profiling technique will get at the real fundamentals of complex conditions such as B-CLL. |
