A new study shows that low-molecular-weight protein biomarkers are bound to larger circulating carrier proteins, which help ferry these smaller protein fragments throughout the body. These protein biomarkers can signal early stage of disease and are more abundant than earlier believed. The research, by scientists at the National Cancer Institute (NCI) - a component of the National Institutes of Health - the Food and Drug Administration, the Howard Hughes Medical Institute, and Northwestern University Medical School, is published in the December 2003/January 2004 issue of Disease Markers*.

In the past, investigators attempting to discover new disease biomarkers present in the blood have discarded the large, most abundant protein molecules before traditional discovery methods were employed. Lead author, Arpita I. Mehta, said, "Our mass spectrometry biomarker analysis is unique because we neither enzymatically treat large proteins to break them down nor do we discard large proteins from our analysis. Thus we can examine what is stuck to these large proteins when we look for cancer biomarkers instead of throwing them out from the beginning."

To evaluate the effectiveness of this method, serum samples from women with ovarian cancer were tested using mass spectrometry. The analysis showed that biomarkers bound to circulating carrier proteins were of the same size as those that had been previously reported and were 100-percent predictive of ovarian cancer in the samples tested. It was not known that the previously reported biomarkers were attached to carrier proteins.

By not discarding the large carrier proteins, biomarkers become more concentrated; as the biomarker is produced, it is captured by the protein rather than being excreted. This raises the measurable concentration of markers by orders of hundreds or even thousands, making development of a clinical testing procedure that could detect cancer at a very early stage in asymptomatic women much more comprehensive.

Lance Liotta, M.D., Ph.D., a co-author and investigator at NCI's Center for Cancer Research, said, "By capturing a much greater number of protein fragments, we no longer are searching for a single protein that may be diagnostic for cancer, but rather a host or combination of protein markers that could be much more accurate."

Emanuel Petricoin, Ph.D., a co-director with Liotta of the NCI-FDA Clinical Proteomics Program, and a co-author on the paper, concurred that " based on this discovery, investigators could uncover thousands of biomarkers never before known to exist in the blood - these carrier proteins are acting as "molecular mops" by just soaking these markers up."

* Mehta AI, Ross S, Lowenthal MS, Fusaro V, Fishman DA, Petricoin EF, and Liotta LA. Biomarker amplification by serum carrier protein binding. Disease Markers,(IOS Press), Vol. 19, pp. 1-10 (2003/04).

Note: On Wednesday, January 28, 2004 from 11 a.m.-1:30 p.m., NIH Campus, Natcher Conference Center, Room F1, Bethesda, Md., the NCI press office will host the sixth science writers' seminar specifically designed for science and medical reporters. Several of the authors of the research highlighted in this Disease Markers article will present their current findings and give extensive background on proteomics research. To attend, please call the NCI press office at (301) 496-6641.

For background on proteomics, please go to: http://cancer.gov/BenchMarks/archives/2002_02/index.html

For more information on cancer, please visit the NCI home page at http://www.cancer.gov.

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