Proteomic mapping of p53 immunogenicity in pancreatic, ovarian, and breast cancers

Benjamin A. Katchman, Rodrigo Barderas, Rizwan Alam, Diego Chowell, Matthew S. Field, Laura J. Esserman, Garrick Wallstrom, Joshua LaBaer, Daniel W. Cramer, Michael A. Hollingsworth, Karen Anderson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Purpose: Mutations in TP53 induce autoantibody immune responses in a subset of cancer patients, which have been proposed as biomarkers for early detection. Here, we investigate the association of p53-specific autoantibodies with multiple tumor subtypes and determine the association with p53 mutation status and epitope specificity. Experimental design: IgG p53 autoantibodies (p53-AAb), were quantified in 412 serum samples using a programmable ELISA assay from patients with serous ovarian, pancreatic adenocarcinoma, and breast cancer. To determine if patients generated mutation-specific autoantibodies we designed a panel of the most relevant 51 p53 point mutant proteins, to be displayed on custom programmable protein microarrays. To determine the epitope specificity we displayed 12 overlapping tiling fragments and 38 N- and C-terminal deletions spanning the length of the wild-type p53 protein. Results: We detected p53-AAb with sensitivities of 58.8% (ovarian), 22% (pancreatic), 32% (triple negative breast cancer), and 10.2% (HER2+ breast cancer) at 94% specificity. Sera with p53-AAb contained broadly reactive autoantibodies to 51 displayed p53 mutant proteins, demonstrating a polyclonal response to common epitopes. All p53-AAb displayed broad polyclonal immune response to both continuous and discontinuous epitopes at the N- and C-terminus as well as the DNA-binding domain. Conclusion and clinical relevance: In this comprehensive analysis, mutations in tumor p53 induce strong, polyclonal autoantibodies with broadly reactive epitope specificity.

Original languageEnglish (US)
Pages (from-to)720-731
Number of pages12
JournalProteomics - Clinical Applications
Volume10
Issue number7
DOIs
StatePublished - Jul 1 2016

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Pancreatic Neoplasms
Autoantibodies
Proteomics
Ovarian Neoplasms
Breast Neoplasms
Epitopes
Mutation
Mutant Proteins
Tumors
Association reactions
Triple Negative Breast Neoplasms
Neoplasms
Protein Array Analysis
Biomarkers
Microarrays
Serum
Design of experiments
Assays
Proteins
Adenocarcinoma

Keywords

  • Antibody mapping
  • Autoantibody
  • Cancer
  • p53
  • Protein array

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Proteomic mapping of p53 immunogenicity in pancreatic, ovarian, and breast cancers. / Katchman, Benjamin A.; Barderas, Rodrigo; Alam, Rizwan; Chowell, Diego; Field, Matthew S.; Esserman, Laura J.; Wallstrom, Garrick; LaBaer, Joshua; Cramer, Daniel W.; Hollingsworth, Michael A.; Anderson, Karen.

In: Proteomics - Clinical Applications, Vol. 10, No. 7, 01.07.2016, p. 720-731.

Research output: Contribution to journalArticle

Katchman, BA, Barderas, R, Alam, R, Chowell, D, Field, MS, Esserman, LJ, Wallstrom, G, LaBaer, J, Cramer, DW, Hollingsworth, MA & Anderson, K 2016, 'Proteomic mapping of p53 immunogenicity in pancreatic, ovarian, and breast cancers' Proteomics - Clinical Applications, vol. 10, no. 7, pp. 720-731. https://doi.org/10.1002/prca.201500096
Katchman BA, Barderas R, Alam R, Chowell D, Field MS, Esserman LJ et al. Proteomic mapping of p53 immunogenicity in pancreatic, ovarian, and breast cancers. Proteomics - Clinical Applications. 2016 Jul 1;10(7):720-731. https://doi.org/10.1002/prca.201500096
Katchman, Benjamin A. ; Barderas, Rodrigo ; Alam, Rizwan ; Chowell, Diego ; Field, Matthew S. ; Esserman, Laura J. ; Wallstrom, Garrick ; LaBaer, Joshua ; Cramer, Daniel W. ; Hollingsworth, Michael A. ; Anderson, Karen. / Proteomic mapping of p53 immunogenicity in pancreatic, ovarian, and breast cancers. In: Proteomics - Clinical Applications. 2016 ; Vol. 10, No. 7. pp. 720-731.
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