Using quantitative seroproteomics to identify antibody biomarkers in pancreatic cancer

Darshil T. Jhaveri, Min Sik Kim, Elizabeth D. Thompson, Lanqing Huang, Rajni Sharma, Alison P. Klein, Lei Zheng, Dung T. Le, Daniel A. Laheru, Akhilesh Pandey, Elizabeth M. Jaffee, Robert A. Anders

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Pancreatic cancer is the fourth leading cause of cancerrelated deaths in the United States. Less than 6% of patients survive beyond the fifth year due to inadequate early diagnostics and ineffective treatment options. Our laboratory has developed an allogeneic, granulocyte-macrophage colonystimulating factor (GM-CSF)-secreting pancreatic cancer vaccine (GVAX) that has been tested in phase II clinical trials. Here, we employed a serum antibodies-based SILAC immunoprecipitation (SASI) approach to identify proteins that elicit an antibody response after vaccination. The SASI approach uses immunoprecipitation with patient-derived antibodies that is coupled to quantitative stable isotope-labeled amino acids in cell culture (SILAC). Using mass spectrometric analysis, we identified more than 150 different proteins that induce an antibody response after vaccination. The regulatory subunit 12A of protein phosphatase 1 (MYPT1 or PPP1R12A), regulatory subunit 8 of the 26S proteasome (PSMC5), and the transferrin receptor (TFRC) were shown to be pancreatic cancer-associated antigens recognized by postvaccination antibodies in the sera of patients with favorable disease-free survival after GVAX therapy. We further interrogated these proteins in over 80 GVAX-treated patients' pancreases and uniformly found a significant increase in the expression of MYPT1, PSMC5, and TFRC in neoplastic compared with nonneoplastic pancreatic ductal epithelium. We show that the novel SASI approach can identify antibody targets specifically expressed in patients with improved disease-free survival after cancer vaccine therapy. These targets need further validation to be considered as possible pancreatic cancer biomarkers.

Original languageEnglish (US)
Pages (from-to)225-233
Number of pages9
JournalCancer Immunology Research
Volume4
Issue number3
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Fingerprint Dive into the research topics of 'Using quantitative seroproteomics to identify antibody biomarkers in pancreatic cancer'. Together they form a unique fingerprint.

  • Cite this

    Jhaveri, D. T., Kim, M. S., Thompson, E. D., Huang, L., Sharma, R., Klein, A. P., Zheng, L., Le, D. T., Laheru, D. A., Pandey, A., Jaffee, E. M., & Anders, R. A. (2016). Using quantitative seroproteomics to identify antibody biomarkers in pancreatic cancer. Cancer Immunology Research, 4(3), 225-233. https://doi.org/10.1158/2326-6066.CIR-15-0200-T