@article{37d2e74137de4f0eba4a548f291857da,
title = "Using quantitative seroproteomics to identify antibody biomarkers in pancreatic cancer",
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.",
author = "Jhaveri, {Darshil T.} and Kim, {Min Sik} and Thompson, {Elizabeth D.} and Lanqing Huang and Rajni Sharma and Klein, {Alison P.} and Lei Zheng and Le, {Dung T.} and Laheru, {Daniel A.} and Akhilesh Pandey and Jaffee, {Elizabeth M.} and Anders, {Robert A.}",
note = "Funding Information: The authors gratefully acknowledge Drs. Christine Iacobuzio-Donahue, Edward Gabrielson, and Peter Argani for providing the TMAs (all Johns Hopkins University School of Medicine). The authors also acknowledge the joint participation by the Adrienne Helis Malvin Medical Research Foundation and the Diana Helis Henry Medical ResearchFoundation through its direct engagement in the continuous active conduct of medical research in conjunction with the Johns Hopkins Hospital, the Johns Hopkins University School of Medicine, and the Foundation's Parkinson's Disease Programs. This work was supported by the NIH K23 CA148964-01 (to L. Zheng), Johns Hopkins School of Medicine Clinical Scientist Award (to L. Zheng), an American Society of Clinical Oncology Young Investigator Award (to L. Zheng), Viragh Foundation and the Skip Viragh Pancreatic Cancer Center at Johns Hopkins (to D. Laheru, E.M. Jaffee, and L. Zheng), The National Pancreas Foundation (to L. Zheng), Lefkofsky Family Foundation (to L. Zheng and E. Jaffee), the NCI SPORE in Gastrointestinal Cancers P50 CA062924 (to E.M. Jaffee, L. Zheng, A. P. Klein, and D Laheru), Lustgarten Foundation (to E.M. Jaffee and L. Zheng), and the Sol Goldman Pancreatic Cancer Center (to L. Zheng), And NIH 5K23 CA163672-02 (to D. T. Le). E.M. Jaffee is the first recipient of the Dana and Albert {"}Cubby{"} Broccoli Endowed Professorship. This study was also supported in part by grant no. S10RR023025 from the High End Instrumentation Program of the NIH, NCI's Clinical Proteomic Tumor Analysis Consortium initiative (U24CA160036), a NIH grant (CA62924), a contract (HHSN268201000032C) from the National Heart, Lung and Blood Institute, and the Sol Goldman Pancreatic Cancer Research Center. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Publisher Copyright: {\textcopyright} 2016 American Association for Cancer Research.",
year = "2016",
month = mar,
doi = "10.1158/2326-6066.CIR-15-0200-T",
language = "English (US)",
volume = "4",
pages = "225--233",
journal = "Cancer immunology research",
issn = "2326-6066",
publisher = "American Association for Cancer Research Inc.",
number = "3",
}