Scientists: New technique identifies molecular 'biomarkers' for disease

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Scientists: New technique identifies molecular 'biomarkers' for

disease

http://www.eurekalert.org/pub_releases/2008-03/uof-snt033108.php

University of Florida chemists are the first to use a new tool to

identify the molecular signatures of serious diseases -- without any

previous knowledge of what these microscopic signatures

or " biomarkers " should look like.

Reported this month in the online edition of the Journal of Proteome

Research, the advance could one day lead to earlier detection and

improved treatment of some types of cancer as well as other diseases.

" With many diseases, the problem has been that we really don't know

what to look for, " said Weihong Tan, a professor of chemistry and the

lead author of the paper. " What we've done is create a technique to

identify the biomarkers despite that limitation. "

Doctors often diagnose cancer and other diseases based on the

appearance of a tumor or a patient's symptoms. While such traditional

methods can be effective, they sometimes identify a disease only

after it is established. For example, clinicians may get tipped off

to the presence of lung cancer – which kills more people than any

other type of cancer – based on visible images of a tumor that appear

on radiological exams of a patient's lungs.

Because earlier detection typically improves outcomes, doctors would

like to spot disease at the molecular level, before it grows or

spreads and manifests itself in more obvious and harmful ways. Given

that diseased cells' molecular structures differ from those of

healthy ones, that approach should be possible, and researchers have

had some success finding such " biomarkers " using antibodies, Tan

said. But despite years of research, biomarkers for most diseases

remain elusive or unreliable, he said.

His group turned to " aptamers, " single-strand chains of DNA or RNA

that recognize and bind to target protein molecules, as a new tool.

His paper reports the first-ever successful use of the aptamers to

discover a molecular biomarker – in this case, one for leukemia.

Tan said his group used cell-SELEX, a process his group developed and

patented.

Researchers create trillions of different varieties of aptamers in a

solution. They then immerse cells known to carry the sought-after

disease in the solution. After an incubation period, they rinse the

cells.

The vast majority of the aptamers wash away, but those with stronger

molecular affinity for the diseased cells remain. The researchers

repeat the process several times, eventually shrinking the pool of

aptamers to as few as 10 to 25 very strongly attached aptamers –

those most closely associated with the diseased cells. Analysis then

reveals these aptamers' molecular structure, as well as the molecular

structure of the cells' biomarkers they bind to.

" As long as the molecules in question are expressed in a

substantially different way on diseased and normal cells, they can be

identified, " Tan said.

Sutphen, associate professor and director of the Genetic

Counseling & Testing Service at the H. Lee Moffitt Cancer Center &

Research Institute in Tampa, said improved diagnosis may not be the

only application of the research.

" The opportunity to identify cancer cell-specific biomarkers and

potentially detect small numbers of cancer cells has many potential

clinical applications, including disease detection, better imaging of

tumors and even potential application for stem cells, " she said.

Other biomarkers have been found for leukemia, but none is

particularly reliable, Tan said. Tan and his colleagues reported

using aptamers to recognize cancer cells in a 2006 paper in the

Proceedings of the National Academy of Sciences. Tan said the latest

paper advances that work by revealing the target biomarkers the

selected aptamers recognize, Tan said. These targets will form a

molecular foundation in understanding diseases, he said.

" In 2006, we did not know what the aptamer recognized on the cancer

cell surface, " he said. " In this current work, we report discovering

these biomarkers, which then form the molecular foundation for us to

understand the cancer and to prepare different molecular tools for

molecular medicine. "

Tan said the research is particularly promising because aptamers are

relatively easy and inexpensive to manufacture compared with

antibodies. " This offers the potential for wider application, " he

said, adding that aptamers could one day be used not only to detect

disease, but also to ferry therapeutic agents to diseased cells.