WEST LAFAYETTE, Ind. — Studies by a Purdue University-led team
have revealed a potential marker for prostate cancer that could be
the starting point for less invasive testing and improved diagnosis
of the disease.
The team used a new analysis technique to create a profile of
the lipids, or fats, found in prostate tissue and discovered a
molecular compound that appears to be useful in identifying
cancerous and precancerous tissue. The profile revealed that
cholesterol sulfate is a compound that is absent in healthy
prostate tissue, but is a major fat found in prostate cancer
tumors.
Graham Cooks, Purdue’s Henry Bohn Hass Distinguished Professor
of Chemistry, and Timothy Ratliff, the Robert Wallace Miller
Director of the Purdue Center for Cancer Research, led the
team.
“It was surprising to find a single compound that is distinctly
present in cancerous tissue and not present in healthy tissue,”
said Cooks, who is co-director of Purdue’s Center for Analytical
Instrumentation Development. “We’ve been able to differentiate
cancerous from healthy tissue using this new method in the past,
but the difference was in the amounts of the same chemical
compounds found in healthy tissue. There was no single
differentiator of which one could say if it was present there was
cancerous tissue.”
Ratliff said this characteristic makes the compound a potential
marker for the disease, which could lead to new blood or urine
tests to screen for prostate cancer.
“Aside from skin cancer, prostate cancer is the most common
cancer in men and is the second leading cause of cancer-related
deaths,” Ratliff said. “Unfortunately, the current screening test
has a significant number of false positives because it uses a
marker that is present with other non-cancerous conditions. As a
result, many men have unnecessary biopsies, which are invasive,
expensive and have the potential to cause infection. This new
compound appears to be highly specific to prostate cancer cells,
which would mean very few false positives.”
The current prostate cancer test screens for a protein called
prostate-specific antigen, or PSA, that is produced by the cells of
the prostate. Elevated levels of PSA in the blood can signify
prostate cancer, but non-cancerous conditions such as an enlarged
or inflamed prostate also cause an increase in its levels, he
said.
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The findings of the study, which was funded by the Purdue
University Center for Cancer Research and the National Institutes
of Health, were published in the journal Analytical
Chemistry.
The study was performed in collaboration with physician
scientists from Indiana University School of Medicine, who
co-authored the paper. They also provided the tissue samples and
pathological analysis of the samples to check the new technique’s
results.
The team used a mass spectrometry analysis technique developed
by Cooks and coworkers called desorption electrospray ionization,
or DESI, to measure and compare the chemical characteristics of 68
samples of normal and cancerous prostate tissue.
Mass spectrometry works by first turning molecules into ions, or
electrically charged versions of themselves, so that they can be
identified by their mass. Conventional mass spectrometry requires
chemical separations, manipulations of samples and containment in a
vacuum chamber for ionization and analysis. The DESI technique
eliminates these requirements by performing the ionization step in
the air or directly on surfaces outside of the mass spectrometers,
making the process much simpler, faster and more applicable to
medical examination or surgical settings.
Cooks’ research team also has developed software that turns the
distribution and intensity of selected ions within a sample into a
computer-generated image, much like what would be seen from a
stained slide under the microscope. This chemical map of the sample
can precisely show the location of cancerous tissue and the borders
of tumors, Cooks said.
Livia Eberlin, co-author of the paper and a graduate student in
Cooks’ group, said the study showed promise in detecting
precancerous lesions, as well.
“The DESI examination was able to distinguish a precancerous
lesion in a small area of a sample made up of mostly healthy
tissue,” Eberlin said. “By evaluating the difference in the
chemistry of cells, this technique can detect differences in
diseased tissue that are otherwise indistinguishable. It could
provide a new tool for pathologists to complement microscopic
examination.”
The team also plans to study differences in the chemistry of
different types of prostate cancer tumors to see if there is a way
to identify which are aggressive and which are not, she said.
Ratliff said the inability to tell the difference between
aggressive and nonaggressive forms of prostate cancer causes
problems in its treatment.
“A nonaggressive form of prostate cancer can be very slow to
progress, and sometimes it is in the best interest of the patient
not to go through rigorous treatments that reduce one’s quality of
life,” he said. “The tests currently used to determine the
probability that the cancer is an aggressive form are not very
accurate, and about 30 percent of patients are misdiagnosed as
having an aggressive form.”
Additional co-authors of the paper include graduate students
Allison Dill and Anthony Costa, and post doctoral researcher Demian
Ifa from Purdue’s Department of Chemistry and the Center for
Analytical Instrumentation Development; Dr. Liang Cheng from the
Indiana University School of Medicine Department of Pathology and
Laboratory Medicine; and Dr. Timothy Masterson and Dr. Michael Koch
from the Indiana University School of Medicine Department of
Urology.
The team is already in the process of performing larger studies
and plans to investigate the biological processes responsible for
the expression of cholesterol sulfate in cancerous tissue.