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.
Background New biomarkers, such as autoantibody signatures,may improve the early detection of prostate cancer.
Methods With a phage-display library derived from prostate-cancertissue, we developed and used phage protein microarrays to analyzeserum samples from 119 patients with prostate cancer and 138controls, with the samples equally divided into training andvalidation sets. A phage-peptide detector that was constructedfrom the training set was evaluated on an independent validationset of 128 serum samples (60 from patients with prostate cancerand 68 from controls).
Results A 22-phage-peptide detector had 88.2 percent specificity(95 percent confidence interval, 0.78 to 0.95) and 81.6 percentsensitivity (95 percent confidence interval, 0.70 to 0.90) indiscriminating between the group with prostate cancer and thecontrol group. This panel of peptides performed better thandid prostate-specific antigen (PSA) in distinguishing betweenthe group with prostate cancer and the control group (area underthe curve for the autoantibody signature, 0.93; 95 percent confidenceinterval, 0.88 to 0.97; area under the curve for PSA, 0.80;95 percent confidence interval, 0.71 to 0.88). Logistic-regressionanalysis revealed that the phage-peptide panel provided additionaldiscriminative power over PSA (P<0.001). Among the 22 phagepeptides used as a detector, 4 were derived from in-frame, namedcoding sequences. The remaining phage peptides were generatedfrom untranslated sequences.
Conclusions Autoantibodies against peptides derived from prostate-cancertissue could be used as the basis for a screening test for prostatecancer.
Source Information
From the Departments of Pathology (X.W., J.Y., A.S., S.V., R.S., D. Giacherio, R.M., A.M.C.), Biostatistics (R.S., D. Ghosh), Urology (J.E.M., K.J.P., J.T.W., A.M.C.), and Internal Medicine (K.J.P.), and the Comprehensive Cancer Center (A.S., S.V., J.E.M., K.J.P., J.T.W., A.M.C.), University of Michigan Medical School, Ann Arbor; and Beth Israel – Deaconess Medical Center (M.G.S.), Dana – Farber Cancer Institute (P.W.K.), and Brigham and Women's Hospital (M.A.R.), Harvard Medical School — all in Boston. Drs. Wang and Yu contributed equally to this article.
Address reprint requests to Dr. Chinnaiyan at the Department of Pathology and Urology, University of Michigan Medical School, 1301 Catherine St., MSI 4237, University of Michigan, Ann Arbor, MI 48109, or at arul{at}umich.edu.
Autoantibodies in Prostate Cancer
Tan E.M., Koziol J. A., Kida Y., Thorat M. A., Badwe R. A., Rocco B., Djavan B., de Cobelli O., Wang X., Ghosh D., Chinnaiyan A. M.
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N Engl J Med 2005;
353:2815-2817, Dec 29, 2005.
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