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.