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Clinical Question: Does new
biomarkers, such as autoantibody signatures may improve the early detection
of prostate cancer?
Bottom Line: Autoantibodies against
peptides derived from prostate-cancer tissue could be used as the basis for
a screening test for prostate cancer.
Reference: Autoantibody Signatures in
Prostate Cancer
Xiaoju Wang, Ph.D., Jianjun Yu, M.S., Arun Sreekumar, Ph.D., Sooryanarayana
Varambally, Ph.D., Ronglai Shen, M.S., Donald Giacherio, Ph.D., Rohit Mehra,
M.D., James E. Montie, M.D., Kenneth J. Pienta, M.D., Martin G. Sanda, M.D.,
Philip W. Kantoff, M.D., Mark A. Rubin, M.D., John T. Wei, M.D., Debashis
Ghosh, Ph.D., and Arul M. Chinnaiyan, M.D., Ph.D. NEJM Volume 353:1224-1235
September 22, 2005 Number 12
Synopsis: Limitations of the
prostate-specific antigen (PSA) test for the early detection of prostate
cancer indicate the need for other means of screening for this neoplasm. The
finding that patients with cancer produce autoantibodies against antigens in
their tumors suggests that such autoantibodies could have diagnostic and
prognostic value. For example, mutant forms of the p53 protein elicit
anti-p53 antibodies in 30 to 40 percent of patients with various types of
cancers. Recently, we found that patients with prostate cancer produce
antibodies against {alpha}-methylacyl-coenzyme A racemase, an overexpressed
protein in epithelial cells in prostate cancer. This autoantibody had 72
percent specificity and 62 percent sensitivity in detecting prostate
cancer.The use of additional prostate-cancer antigens could improve the
sensitivity and specificity of an autoantibody-based screening test for
prostate cancer.
With a phage-display library derived from prostate-cancer tissue, we
developed and used phage protein microarrays to analyze serum samples from
119 patients with prostate cancer and 138 controls, with the samples equally
divided into training and validation sets. A phage-peptide detector that was
constructed from the training set was evaluated on an independent validation
set of 128 serum samples (60 from patients with prostate cancer and 68 from
controls). A 22-phage-peptide detector had 88.2 percent specificity (95
percent confidence interval, 0.78 to 0.95) and 81.6 percent sensitivity (95
percent confidence interval, 0.70 to 0.90) in discriminating between the
group with prostate cancer and the control group. This panel of peptides
performed better than did prostate-specific antigen (PSA) in distinguishing
between the group with prostate cancer and the control group (area under the
curve for the autoantibody signature, 0.93; 95 percent confidence interval,
0.88 to 0.97; area under the curve for PSA, 0.80; 95 percent confidence
interval, 0.71 to 0.88). Logistic-regression analysis revealed that the
phage-peptide panel provided additional discriminative power over PSA
(P<0.001). Among the 22 phage peptides used as a detector, 4 were derived
from in-frame, named coding sequences. The remaining phage peptides were
generated from untranslated sequences.
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