Cancer immunomics: using autoantibody signatures in the early detection of prostate cancer.

Prostate cancer remains the most common malignancy among men and the second leading cause of cancer death of men in the United States. Although measurement of prostate-specific antigen (PSA) has led to earlier detection of many prostate cancers, new serum biomarkers are still needed to improve the accuracy of prostate cancer detection. Considerable evidence has shown that an immune response in the form of autoantibodies to various tumor antigens develops in many patients with cancer. By using phage-epitope microarray analysis, we were able to identify peptides expressed by prostate cancer tissue, which commonly induce formation of autoantibodies in the sera of patients with prostate cancer. Using a panel of 22 peptides, we were able to detect prostate cancer with a specificity of 88.2% and a sensitivity of 81.6%. These results were significantly better than PSA, especially among men with a PSA between 4 and 10 ng/ml. Measurement of the immune response to prostate cancer, as well as other malignancies, has the potential to improve significantly the detection of these cancers and possibly assist in the determination of prognosis.

[1]  S. Reed,et al.  P504S: A New Molecular Marker for the Detection of Prostate Carcinoma , 2001, The American journal of surgical pathology.

[2]  C C Schulman,et al.  PSA, PSA density, PSA density of transition zone, free/total PSA ratio, and PSA velocity for early detection of prostate cancer in men with serum PSA 2.5 to 4.0 ng/mL. , 1999, Urology.

[3]  Yao-Tseng Chen,et al.  Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Pfreundschuh,et al.  Human neoplasms elicit multiple specific immune responses in the autologous host. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Trent,et al.  α-methylacyl-CoA racemase: A new molecular marker for prostate cancer , 2002 .

[6]  A W Partin,et al.  The role of PSA and percent free PSA for staging and prognosis prediction in clinically localized prostate cancer. , 1998, Seminars in urologic oncology.

[7]  Debashis Ghosh,et al.  Autoantibody signatures in prostate cancer. , 2005, The New England journal of medicine.

[8]  Lloyd J. Old,et al.  A Survey of the Humoral Immune Response of Cancer Patients to a Panel of Human Tumor Antigens , 1998, The Journal of experimental medicine.

[9]  S M Hanash,et al.  An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[10]  G. Ronquist,et al.  Autoantibodies to Prostasomes as New Markers for Prostate Cancer , 2001, Upsala journal of medical sciences.

[11]  A. Stromberg,et al.  Antibodies to HSP70 and HSP90 in serum in non-small cell lung cancer patients. , 2003, Cancer detection and prevention.

[12]  Kim-Anh Do,et al.  Fingerprinting the circulating repertoire of antibodies from cancer patients , 2003, Nature Biotechnology.

[13]  Debashis Ghosh,et al.  Humoral Immune Response to α-Methylacyl-CoA Racemase and Prostate Cancer , 2004 .

[14]  C. Pellat-deceunynck,et al.  Tumour‐associated antigens in multiple myeloma , 2003, British journal of haematology.

[15]  Lloyd J. Old,et al.  New Paths in Human Cancer Serology , 1998, The Journal of experimental medicine.

[16]  Franco Felici,et al.  Identification of tumor‐associated antigens by screening phage‐displayed human cDNA libraries with sera from tumor patients , 2003, International journal of cancer.

[17]  T. Soussi,et al.  p53 Antibodies in the sera of patients with various types of cancer: a review. , 2000, Cancer research.

[18]  Debashis Ghosh,et al.  alpha-Methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. , 2002, JAMA.

[19]  E. Crawford,et al.  Epidemiology of prostate cancer. , 2003, Urology.