|Researchers Discover Protein Signatures for Prostate Cancer
That Could Improve Diagnosis of Early Disease
A new study shows that testing blood samples for antibodies that target prostate
cancer cells may help identify patients with early stages of the disease. In
the September 22, 2005, issue of New England Journal of Medicine*, researchers
report the findings may lead to a new test that could complement the prostate
specific antigen (PSA) test in detecting early stage prostate cancer. The study
was supported by the Early Detection Research Network (EDRN), an initiative of
the National Cancer Institute (NCI), part of the National Institutes of Health.
Previous studies have found that men with normal blood levels of PSA (4.0 ng/ml
or less) can have prostate cancer**. Furthermore, PSA-based prostate cancer screening
has a high rate of false-positive results (up to 80 percent). Therefore, scientists
have been looking for additional ways to adequately screen for early disease.
“Using PSA testing alone results in millions of dollars being spent on prostate
biopsies due to false positive results. We don’t yet know if our new findings
will save lives, but there could be a major cost saving by decreasing the number
of prostate biopsies performed every year,” said Sudhir Srivastava, Ph.D., Chief,
Cancer Biomarkers Research Program and Director for the EDRN.
The panel of 22 target proteins identified in this study showed an 88.2 percent
specificity value for prostate cancer, which indicates the proportion of those
tested who did not have cancer and were correctly identified as being free of
disease. The test also showed an 81.6 percent sensitivity value, indicating the
proportion of those patients with cancer that were correctly diagnosed as having
Scientists know that cancer patients produce antibodies to proteins, called
antigens, which are present on the surface of tumor cells. Antibodies themselves
are proteins produced by immune cells to help fight and destroy viruses, bacteria,
and other foreign substances that invade the body. As a cancer cell grows, normal
antigens can be presented on a cell surface in a different way. The body then
recognizes these antigens as foreign and produces antibodies to them. These particular
antibodies are termed autoantibodies, because they react to a substance produced
by the body itself.
"In this study, we took advantage of the body's own immune system as a detector
of prostate cancer,” said Arul Chinnaiyan, M.D., Ph.D., study leader, University
of Michigan Medical School, Ann Arbor. “While the present study focused on the
detection of prostate cancer, this general approach has potential to be developed
for other cancers as well as for other human diseases that in some way perturb
the immune system."
The use of autoantibody signatures may be useful in combination with PSA testing
in reducing the number of false negative and false positive tests obtained then
when using PSA testing alone. Statistical analysis of these results shows that
the protein panel performed better in distinguishing between prostate cancer
patients and controls than the PSA test. The panel of 22 proteins predicted the
presence of cancer accurately 92.7 percent of the time, while PSA predicted the
presence of cancer only 79.6 percent of the time. The use of autoantibody signatures
may be most informative in assessing the need for a biopsy in patients with PSA
values of 10ng/ml or less.
“Identification of autoantibodies is an exciting area of research. We are also
looking to see if the autoantibodies produced against prostate cancer cells are
specific only to this disease,” said Srivastava. “Knowledge of whether antibodies
are specific to particular organs will be important when considering a design
for any new test.”
A total of 257 blood samples were tested for novel prostate cancer autoantibodies;
blood samples from 119 patients with prostate cancer were studied prior to surgery
and 138 samples were from patients without prostate cancer. Among the 22 peptides
found, the genes that code four of them were identified: eIF4G1, BRD2, RPL13a,
Collaborators supported by the EDRN will further analyze the peptide panel test.
Both the reproducibility of this study protocol and new blood samples will be
used to validate the peptide panel. For clinical application to occur, the test
will need to be validated in different populations and at various EDRN testing
sites; a process that is being planned.
For more information about cancer, visit the NCI Web site at http://www.cancer.gov or
call NCI's Cancer Information Service at 1-800-4 CANCER (1-800-422-6237).
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Agency — includes 27 Institutes and Centers and is a component of
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agency for conducting and supporting basic, clinical, and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.