Protein Microarray Signature of Autoantibody Biomarkers for the Early Detection of Breast Cancer

J Proteome Res. 2011 Jan 7;10(1):85-96. doi: 10.1021/pr100686b. Epub 2010 Nov 23.

Abstract

Cancer patients spontaneously generate autoantibodies (AAb) to tumor-derived proteins. To detect AAb, we have probed novel high-density custom protein microarrays (NAPPA) expressing 4988 candidate tumor antigens with sera from patients with early stage breast cancer (IBC), and bound IgG was measured. We used a three-phase serial screening approach. First, a prescreen was performed to eliminate uninformative antigens. Sera from stage I-III IBC (n = 53) and healthy women (n = 53) were screened for AAb to all 4988 protein antigens. Antigens were selected if the 95th percentile of signal of cases and controls were significantly different (p < 0.05) and if the number of cases with signals above the 95th percentile of controls was significant (p < 0.05). These 761 antigens were screened using an independent set of IBC sera (n = 51) and sera from women with benign breast disease (BBD) (n = 39). From these, 119 antigens had a partial area under the ROC curve (p < 0.05), with sensitivities ranging from 9-40% at >91% specificity. Twenty-eight of these antigens were confirmed using an independent serum cohort (n = 51 cases/38 controls, p < 0.05). Using all 28 AAb, a classifier was identified with a sensitivity of 80.8% and a specificity of 61.6% (AUC = 0.756). These are potential biomarkers for the early detection of breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Autoantibodies / blood*
  • Autoantibodies / genetics
  • Autoantibodies / metabolism
  • Biomarkers / blood*
  • Biomarkers / metabolism
  • Breast Neoplasms / blood
  • Breast Neoplasms / diagnosis*
  • Case-Control Studies
  • Female
  • Gene Expression Profiling
  • Humans
  • Oligonucleotide Array Sequence Analysis / methods*
  • Protein Array Analysis / methods*
  • Proteomics / methods*
  • ROC Curve
  • Regression Analysis
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Vacuolar Proton-Translocating ATPases / blood
  • Vacuolar Proton-Translocating ATPases / genetics
  • Vacuolar Proton-Translocating ATPases / metabolism

Substances

  • ATP6AP1 protein, human
  • Antigens, Neoplasm
  • Autoantibodies
  • Biomarkers
  • Vacuolar Proton-Translocating ATPases