Identification of tumor antigens that elicit a humoral immune response in breast cancer patients' sera by serological proteome analysis (SERPA)

Clin Chim Acta. 2008 Jul 17;393(2):95-102. doi: 10.1016/j.cca.2008.03.017. Epub 2008 Mar 27.

Abstract

Background: In this study we applied a serological proteomics-based approach (SERPA) to identify tumor antigens that commonly induce a humoral immune response in patients with infiltrating ductal breast carcinomas.

Methods: Sera obtained at the time of diagnosis from 40 patients with invasive breast cancer and 42 healthy controls were screened individually for the presence of IgG antibodies to MCF-7 cell line proteins. Immunoreactive proteins were isolated and subsequently identified by MALDI-TOF mass spectrometry.

Results: We identified 26 proteins that reacted with antibodies in the sera from breast cancer patients. Among these antigens, a significantly higher frequency occurs against the molecular chaperone HSP60, the tumor suppressor prohibitin, beta-tubulin, the haptoglobin-related protein and peroxiredoxin-2. Immunoreactivity to hnRNPK, Mn-SOD and F1-ATPase was also clearly detected in the patients group, whereas scarcely in control sera. By contrast, two other antigens identified as cytokeratins 8 and 18, as well as, F1-actin were found to elicit humoral immune responses in both control and breast cancer patients' sera.

Conclusions: The immunoproteomic approach implemented here offers a powerful tool for determining novel tumor antigens that elicit a humoral immune response in patients with invasive breast cancer. These antigens and/or their related circulating antibodies may display clinical usefulness as potential diagnostic markers and provide a means for a better understanding of the molecular mechanisms underlying breast cancer development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Antibodies, Neoplasm / biosynthesis*
  • Antigens, Neoplasm / immunology*
  • Blood Proteins / chemistry
  • Blood Proteins / metabolism*
  • Breast Neoplasms / blood
  • Breast Neoplasms / immunology*
  • Cell Line, Tumor
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Molecular Sequence Data
  • Proteome*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • Blood Proteins
  • Proteome