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 prostate cancer.
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 these cells. 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 more useful in combination with PSA
testing in reducing the number of false-negative and false-positive tests
obtained than 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, and RPL22***.
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).
* Wang X, Yu J, Sreekumar A, Varambally S, Shen R, Giacherio D, Mehra R, Montie
JE, Pienta KJ, Sanda MG, Mantoff PW, Rubin MA, Wei JT, Ghosh D, Chinnaiyan AM.
Autoantibody Signatures in Prostate Cancer. New England Journal of Medicine,
September 22, 2005: 353 (12): 16-27.
** Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian
LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA. Prevalence of
Prostate Cancer among Men with a Prostate-Specific Antigen Level Less Than or
Equal to 4.0 ng per Milliliter. New England Journal of Medicine, May 27, 2004;
350 (22): 2239-2246.
*** eIF4G1 (eukaryotic translation initiation factor 4 gamma 1), BRD2
(bromodomain containing 2), RPL13a (ribosomal protein L13a), and RPL22
(ribosomal protein L22).
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