Summer 2004

“Fingerprinting” Cancer May Save Lives

Ovarian cancer…prostate cancer…breast cancer. Just hearing the names of these top killers can send a chill down your spine. While detecting such diseases early can help increase survival rates, they are not always easy to detect.


Our scientists at the National Cancer Institute-Frederick, however, are developing ways to better detect a wide range of diseases, including cancer, behavioral disorders, and neurodegenerative diseases, using proteomics — the study of all proteins in living cells.

For example, we are embarked on a clinical study (through our Proteomics Clinical Reference Laboratory) to obtain clinical validation for a potentially revolutionary diagnostic test. Developed to spot recurrence of ovarian cancer, the test uses pattern recognition algorithms to detect hidden sub-patterns in mass spectra of proteins in blood serum. The patterns represent ''fingerprints" of the disease in an early stage. (More than 95% of women diagnosed with ovarian cancer at an early stage have an excellent prognosis for survival.)

Beyond identifying the presence of ovarian cancer, by matching specific proteomic patterns to a particular stage, the test we helped develop may allow researchers to determine how far the disease has progressed. In fact, the test allows researchers to visualize an entire set of proteins in a single view, as well as zoom in and out to focus on regions of interest within the data. This reduces the risk or error and increases efficiency in analyzing large sets of proteins.

In addition, researchers in our laboratory of Proteomics and Analytical Technologies crafted a multistep procedure for separating proteins derived from blood serum prior to the type of mass spectroscopy described above. (Mass spectroscopy creates patterns of protein fragments for analysis.)

This involved using several separation methods — called isoelectric focusing and chromatography — to better identify proteins, including ones that were errant. (Like buoys afloat in a yellow-tinged ocean warning of danger, errant proteins in blood serum can signal cancer.)

The separation methods, based on the size, electric charge, and other chemical properties that differ between proteins, allowed our researchers to weed out abundant, common proteins — without removing highly important low-abundance proteins — and identify more than 1,800 proteins. (In mouse serum, a highly important model for cancer studies, we have identified more than 4,300 proteins.)

"These studies will be carried further with a highly sophisticated Fourier Transform Ion Cyclotron Mass Spectrometer that we have just obtained," according to Dr. Joseph Kates, Director, Research Technology Program at SAIC-Frederick. "That will increase the sensitivity by about two orders of magnitude enabling detection of protein in serum in the attomolar range."

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