title: Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer.
abstract: In response to an urgent need for improved diagnostic and predictive serum biomarkers for management of metastatic prostate cancer, we used phage display fingerprinting to analyze sequentially acquired serum samples from a patient with advancing prostate cancer. We identified a peptide ligand, CTFAGSSC, demonstrating an increased recovery frequency over time. Serum antibody reactivity to this peptide epitope increased in the index patient, in parallel with development of deteriorating symptoms. The antigen mimicking the peptide epitope was identified as alpha-2-Heremans-Schmid glycoprotein, also known as fetuin-A. Metastatic prostate cancer cell lines and bone metastasis samples displayed robust fetuin-A expression, and we demonstrated serum immune reactivity to fetuin-A with concomitant development of metastatic castrate-resistant disease in a large cohort of prostate cancer patients. Whereas fetuin-A is an established tumor antigen in several types of cancer, including breast cancer, glioblastoma, and pancreas cancer, this report is to our knowledge the first study implicating fetuin-A in prostate cancer and indicating that autoantibodies specific for fetuin-A show utility as a prognostic indicator for prostate cancer patients prone to progress to metastatic disease.
authors: Departments of Genitourinary Medical Oncology.
authors: Paul J
authors: PJ
authors: Mintz
authors: University of New Mexico Cancer Center and Divisions of Molecular Medicine, and.
authors: Anna Cecilia
authors: AC
authors: Rietz
authors: University of New Mexico Cancer Center and Divisions of Molecular Medicine, and.
authors: Marina
authors: M
authors: Cardó-Vila
authors: David H. Koch Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
authors: Michael G
authors: MG
authors: Ozawa
authors: David H. Koch Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
authors: Eleonora
authors: E
authors: Dondossola
authors: Biostatistics, and.
authors: Kim-Anh
authors: KA
authors: Do
authors: Departments of Genitourinary Medical Oncology.
authors: Jeri
authors: J
authors: Kim
authors: Pathology and.
authors: Patricia
authors: P
authors: Troncoso
authors: Departments of Genitourinary Medical Oncology.
authors: Christopher J
authors: CJ
authors: Logothetis
authors: Harvard Medical School and Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215; and richard_sidman@hms.harvard.edu rpasqual@salud.unm.edu warap@salud.unm.edu.
authors: Richard L
authors: RL
authors: Sidman
authors: University of New Mexico Cancer Center and Divisions of Molecular Medicine, and richard_sidman@hms.harvard.edu rpasqual@salud.unm.edu warap@salud.unm.edu.
authors: Renata
authors: R
authors: Pasqualini
authors: University of New Mexico Cancer Center and Divisions of Hematology and Medical Oncology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131 richard_sidman@hms.harvard.edu rpasqual@salud.unm.edu warap@salud.unm.edu.
authors: Wadih
authors: W
authors: Arap
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D045744:Cell Line, Tumor; D061505:Cell Surface Display Techniques; D020650:Combinatorial Chemistry Techniques; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D010449:Peptide Mapping; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology; D060749:alpha-2-HS-Glycoprotein / Q000276:immunology
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D010455:Peptides; D060749:alpha-2-HS-Glycoprotein
keywords: cancer biomarker; peptide library; phage display; prostate cancer