Using quantitative seroproteomics to identify antibody biomarkers in pancreatic cancer

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

Research output: Contribution to journalArticle

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

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Pancreatic Neoplasms
Biomarkers
Immunoprecipitation
Antibodies
Cancer Vaccines
Transferrin Receptors
Serum
Isotopes
Disease-Free Survival
Antibody Formation
Vaccination
Cell Culture Techniques
Protein Phosphatase 1
Amino Acids
Active Immunotherapy
Phase II Clinical Trials
Proteins
Tumor Biomarkers
Granulocytes
Pancreas

ASJC Scopus subject areas

  • Cancer Research
  • Immunology

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Using quantitative seroproteomics to identify antibody biomarkers in pancreatic cancer. / Jhaveri, Darshil T.; Kim, Min Sik; Thompson, Elizabeth; Huang, Lanqing; Sharma, Rajni; Klein, Alison; Zheng, Lei; Le, Dung; Laheru, Daniel; Pandey, Akhilesh; Jaffee, Elizabeth; Anders, Robert A.

In: Cancer immunology research, Vol. 4, No. 3, 01.03.2016, p. 225-233.

Research output: Contribution to journalArticle

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