Quantitative proteomics investigation of pancreatic intraepithelial neoplasia

Sheng Pan, Ru Chen, Beth Ann Reimei, David A. Crispin, Hamid Mirzaei, Kelly Cooke, Joshua F. Coleman, Zhaoli Lane, Mary P. Bronner, David R. Goodlett, Martin W. McIntosh, William Traverso, Ruedi Aebersold, Teresa A. Brentnall

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Patients with pancreatic cancer are usually diagnosed at late stages, when the disease is incurable. Pancreatic intraepithelial neoplasia (PanIN) 3 is believed to be the immediate precursor lesion of pancreatic adenocarcinoma, and would be an ideal stage to diagnose patients, when intervention and cure are possible and patients are curable. In this study, we used quantitative proteomics to identify dysregulated proteins in PanIN 3 lesions. Altogether, over 200 dysregulated proteins were identified in the PanIN 3 tissues, with a minimum of a 1.75-fold change compared with the proteins in normal pancreas. These dysregulated PanIN 3 proteins play roles in cell motility, the inflammatory response, the blood clotting cascade, the cell cycle and its regulation, and protein degradation. Further network analysis of the proteins identified c-MYC as an important regulatory protein in PanIN 3 lesions. Finally, three of the overexpressed proteins, laminin beta-1, galectin-1, and actinin-4 were validated by immunohistochemistry analysis. All three of these proteins were overexpressed in the stroma or ductal epithelial cells of advanced PanIN lesions as well as in pancreatic cancer tissue. Our findings suggest that these three proteins may be useful as biomarkers for advanced PanIN and pancreatic cancer if further validated. The dysregulated proteins identified in this study may assist in the selection of candidates for future development of biomarkers for detecting early and curable pancreatic neoplasia.

Original languageEnglish (US)
Pages (from-to)1132-1144
Number of pages13
JournalELECTROPHORESIS
Volume30
Issue number7
DOIs
StatePublished - Jun 1 2009

Keywords

  • Immunohistochemistry
  • MS
  • Pancreatic cancer
  • Pancreatic intraepithelial neoplasia
  • Proteomics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Quantitative proteomics investigation of pancreatic intraepithelial neoplasia'. Together they form a unique fingerprint.

  • Cite this

    Pan, S., Chen, R., Reimei, B. A., Crispin, D. A., Mirzaei, H., Cooke, K., Coleman, J. F., Lane, Z., Bronner, M. P., Goodlett, D. R., McIntosh, M. W., Traverso, W., Aebersold, R., & Brentnall, T. A. (2009). Quantitative proteomics investigation of pancreatic intraepithelial neoplasia. ELECTROPHORESIS, 30(7), 1132-1144. https://doi.org/10.1002/elps.200800752