Autoantibody signatures in prostate cancer

被引:464
作者
Wang, XJ
Yu, JJ
Sreekumar, A
Varambally, S
Shen, RL
Giacherio, D
Mehra, R
Montie, JE
Pienta, KJ
Sanda, MG
Kantoff, PW
Rubin, MA
Wei, JT
Ghosh, D
Chinnaiyan, AM
机构
[1] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA
[2] Univ Michigan, Sch Med, Dept Biostat, Ann Arbor, MI USA
[3] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA
[4] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA
[5] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI USA
[6] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA
[7] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
[8] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA
关键词
D O I
10.1056/NEJMoa051931
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1224 / 1235
页数:12
相关论文
共 33 条
[1]   An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer [J].
Brichory, FM ;
Misek, DE ;
Yim, AM ;
Krause, MC ;
Giordano, TJ ;
Beer, DG ;
Hanash, SM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (17) :9824-9829
[2]  
CATALONA WJ, 1991, NEW ENGL J MED, V325, P1324
[3]   Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library [J].
Chen, YT ;
Güre, AO ;
Tsang, S ;
Stockert, E ;
Jäger, E ;
Knuth, A ;
Old, LJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (12) :6919-6923
[4]  
Cohen Lorenzo, 2003, Cancer Epidemiology Biomarkers & Prevention, V12, P610
[5]  
Dennis LK, 2000, PROSTATE, V42, P247
[6]   Delineation of prognostic biomarkers in prostate cancer [J].
Dhanasekaran, SM ;
Barrette, TR ;
Ghosh, D ;
Shah, R ;
Varambally, S ;
Kurachi, K ;
Pienta, KJ ;
Rubin, MA ;
Chinnaiyan, AM .
NATURE, 2001, 412 (6849) :822-826
[7]   Autoantibodies to annexin XI-A and other autoantigens in the diagnosis of breast cancer [J].
Fernández-Madrid, F ;
Tang, NM ;
Alansari, H ;
Granda, JL ;
Tait, L ;
Amirikia, KC ;
Moroianu, M ;
Wang, XJ ;
Karvonen, RL .
CANCER RESEARCH, 2004, 64 (15) :5089-5096
[8]   How many samples are needed to build a classifier: a general sequential approach [J].
Fu, WJJ ;
Dougherty, ER ;
Mallick, B ;
Carroll, RJ .
BIOINFORMATICS, 2005, 21 (01) :63-70
[9]   Cancer statistics, 2004 [J].
Jemal, A ;
Tiwari, RC ;
Murray, T ;
Ghafoor, A ;
Samuels, A ;
Ward, E ;
Feuer, EJ ;
Thun, MJ .
CA-A CANCER JOURNAL FOR CLINICIANS, 2004, 54 (01) :8-29
[10]   P504S - A new molecular marker for the detection of prostate carcinoma [J].
Jiang, Z ;
Woda, BA ;
Rock, KL ;
Xu, YD ;
Savas, L ;
Khan, A ;
Pihan, G ;
Cai, F ;
Babcook, JS ;
Rathanaswami, P ;
Reed, SG ;
Xu, JC ;
Fanger, GR .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2001, 25 (11) :1397-1404