Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer

Paul J. Mintz, Anna Cecilia Rietz, Marina Cardó-Vila, Michael G. Ozawa, Eleonora Dondossola, Kim Anh Do, Jeri Kim, Patricia Troncoso, Christopher J. Logothetis, Richard L. Sidman, Renata Pasqualini, Wadih Arap

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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 castrateresistant 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.

Original languageEnglish (US)
Pages (from-to)2515-2520
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number8
DOIs
StatePublished - Feb 24 2015
Externally publishedYes

Keywords

  • Cancer biomarker
  • Peptide library
  • Phage display
  • Prostate cancer

ASJC Scopus subject areas

  • General

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