Autoantibody signatures in prostate cancer.
BACKGROUND
New biomarkers, such as autoantibody signatures, may improve the early detection of prostate cancer.


METHODS
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).


RESULTS
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.


CONCLUSIONS
Autoantibodies against peptides derived from prostate-cancer tissue could be used as the basis for a screening test for prostate cancer.
Wang
Xiaoju
X
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Yu
Jianjun
J
Sreekumar
Arun
A
Varambally
Sooryanarayana
S
Shen
Ronglai
R
Giacherio
Donald
D
Mehra
Rohit
R
Montie
James E
JE
Pienta
Kenneth J
KJ
Sanda
Martin G
MG
Kantoff
Philip W
PW
Rubin
Mark A
MA
Wei
John T
JT
Ghosh
Debashis
D
Chinnaiyan
Arul M
AM
D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019151:Peptide Library; D010455:Peptides / Q000276:immunology*; D011467:Prostate / Q000276:immunology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000276:immunology*; D040081:Protein Array Analysis; D012680:Sensitivity and Specificity
D001323:Autoantibodies; D015415:Biomarkers; D014408:Biomarkers, Tumor; D019151:Peptide Library; D010455:Peptides