Plasma Autoantibodies Associated with Basal-like Breast Cancers

Cancer Epidemiol Biomarkers Prev. 2015 Sep;24(9):1332-40. doi: 10.1158/1055-9965.EPI-15-0047. Epub 2015 Jun 12.

Abstract

Background: Basal-like breast cancer (BLBC) is a rare aggressive subtype that is less likely to be detected through mammographic screening. Identification of circulating markers associated with BLBC could have promise in detecting and managing this deadly disease.

Methods: Using samples from the Polish Breast Cancer study, a high-quality population-based case-control study of breast cancer, we screened 10,000 antigens on protein arrays using 45 BLBC patients and 45 controls, and identified 748 promising plasma autoantibodies (AAbs) associated with BLBC. ELISA assays of promising markers were performed on a total of 145 BLBC cases and 145 age-matched controls. Sensitivities at 98% specificity were calculated and a BLBC classifier was constructed.

Results: We identified 13 AAbs (CTAG1B, CTAG2, TP53, RNF216, PPHLN1, PIP4K2C, ZBTB16, TAS2R8, WBP2NL, DOK2, PSRC1, MN1, TRIM21) that distinguished BLBC from controls with 33% sensitivity and 98% specificity. We also discovered a strong association of TP53 AAb with its protein expression (P = 0.009) in BLBC patients. In addition, MN1 and TP53 AAbs were associated with worse survival [MN1 AAb marker HR = 2.25, 95% confidence interval (CI), 1.03-4.91; P = 0.04; TP53, HR = 2.02, 95% CI, 1.06-3.85; P = 0.03]. We found limited evidence that AAb levels differed by demographic characteristics.

Conclusions: These AAbs warrant further investigation in clinical studies to determine their value for further understanding the biology of BLBC and possible detection.

Impact: Our study identifies 13 AAb markers associated specifically with BLBC and may improve detection or management of this deadly disease.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Adult
  • Aged
  • Antigens, Neoplasm / immunology
  • Antigens, Surface / immunology
  • Autoantibodies / blood*
  • Biomarkers, Tumor / blood*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Carrier Proteins / immunology
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Kruppel-Like Transcription Factors / immunology
  • Membrane Proteins / immunology
  • Middle Aged
  • Nuclear Proteins / immunology
  • Phosphoproteins / immunology
  • Poland
  • Promyelocytic Leukemia Zinc Finger Protein
  • Protein Array Analysis
  • RNA, Messenger / blood*
  • Receptors, Cell Surface / immunology
  • Receptors, G-Protein-Coupled
  • Ribonucleoproteins / immunology
  • Seminal Plasma Proteins / immunology
  • Sensitivity and Specificity
  • Survival Rate
  • Trans-Activators
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / immunology*
  • Tumor Suppressor Proteins / immunology
  • Ubiquitin-Protein Ligases / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Neoplasm
  • Antigens, Surface
  • Autoantibodies
  • Biomarkers, Tumor
  • CTAG1B protein, human
  • CTAG2 protein, human
  • Carrier Proteins
  • DOK2 protein, human
  • Kruppel-Like Transcription Factors
  • MN1 protein, human
  • Membrane Proteins
  • Nuclear Proteins
  • PPHLN1 protein, human
  • PSRC1 protein, human
  • Phosphoproteins
  • Promyelocytic Leukemia Zinc Finger Protein
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Ribonucleoproteins
  • SS-A antigen
  • Seminal Plasma Proteins
  • TAS2R8 protein, human
  • TP53 protein, human
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • WBP2NL protein, human
  • ZBTB16 protein, human
  • RNF216 protein, human
  • Ubiquitin-Protein Ligases