Autoantibody signature for the serologic detection of ovarian cancer

J Proteome Res. 2015 Jan 2;14(1):578-86. doi: 10.1021/pr500908n. Epub 2014 Nov 17.

Abstract

Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins that are potential biomarkers for early detection. To detect AAb, we probed high-density programmable protein microarrays (NAPPA) expressing 5177 candidate tumor antigens with sera from patients with serous ovarian cancer (n = 34 cases/30 controls) and measured bound IgG. Of these, 741 antigens were selected and probed with an independent set of ovarian cancer sera (n = 60 cases/60 controls). Twelve potential autoantigens were identified with sensitivities ranging from 13 to 22% at >93% specificity. These were retested using a Luminex bead array using 60 cases and 60 controls, with sensitivities ranging from 0 to 31.7% at 95% specificity. Three AAb (p53, PTPRA, and PTGFR) had area under the curve (AUC) levels >60% (p < 0.01), with the partial AUC (SPAUC) over 5 times greater than for a nondiscriminating test (p < 0.01). Using a panel of the top three AAb (p53, PTPRA, and PTGFR), if at least two AAb were positive, then the sensitivity was 23.3% at 98.3% specificity. AAb to at least one of these top three antigens were also detected in 7/20 sera (35%) of patients with low CA 125 levels and 0/15 controls. AAb to p53, PTPRA, and PTGFR are potential biomarkers for the early detection of ovarian cancer.

Keywords: Ovarian cancer; autoantibodies; biomarker; protein microarrays; proteomics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autoantibodies / blood*
  • Biomarkers, Tumor / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • High-Throughput Screening Assays / methods
  • Humans
  • Immunoglobulin G / metabolism
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / diagnosis*
  • Protein Array Analysis
  • Proteomics / methods*
  • Regression Analysis
  • Sensitivity and Specificity

Substances

  • Autoantibodies
  • Biomarkers, Tumor
  • Immunoglobulin G