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Abstract
Pancreatic cancer is a rapidly fatal disease, and there is an urgent need for early detection markers and novel therapeutic targets. The current study has used a proteomic approach of two-dimensional (2D) gel electrophoresis and mass spectrometry (MS) to identify differentially expressed proteins in six cases of pancreatic adenocarcinoma, two normal adjacent tissues, seven cases of pancreatitis, and six normal pancreatic tissues. Protein extracts of individual sample and pooled samples of each type of tissues were separated on 2D gels using two different pH ranges. Differentially expressed protein spots were in-gel digested and identified by MS. Forty proteins were identified, of which five [i.e., alpha-amylase; copper zinc superoxide dismutase; protein disulfide isomerase, pancreatic; tropomyosin 2 (TM2); and galectin-1] had been associated previously with pancreatic disease in gene expression studies. The identified proteins include antioxidant enzymes, chaperones and/or chaperone-like proteins, calcium-binding proteins, proteases, signal transduction proteins, and extracellular matrix proteins. Among these proteins, annexin A4, cyclophilin A, cathepsin D, galectin-1, 14-3-3zeta, alpha-enolase, peroxiredoxin I, TM2, and S100A8 were specifically overexpressed in tumors compared with normal and pancreatitis tissues. Differential expression of some of the identified proteins was further confirmed by Western blot analyses and/or immunohistochemical analysis. These results show the value of a proteomic approach in identifying potential markers for early diagnosis and therapeutic manipulation. The newly identified proteins in pancreatic tumors may eventually serve as diagnostic markers or therapeutic targets.
Highlights
Our study used 2D PAGE followed by mass spectrometry (MS) and database search to identify 40 proteins differentially expressed in pancreatic adenocar-Despite tremendous advances in our understanding of the molecular basis of pancreatic cancer, substantial gaps remain in our understanding of disease pathogenesis and in the development of effective strategies for early diagnosis and treatment
Normal pancreatic tissues from patients with diseases not related to the pancreas (n ϭ 6), pancreatic tissues from patients with chronic pancreatitis (n ϭ 7), pancreatic ductal adenocarcinomas (n ϭ 6), and normal adjacent tissues (n ϭ 2) were obtained frozen from the National Cancer Institute Human Tissue Network
Additional pancreatic tumors and pancreatic adenocarcinoma cell lines used in the validation tests were obtained from the National Cancer Institute Human Tissue Network and American Type Culture Collection (Manassas, VA), respectively
Summary
Despite tremendous advances in our understanding of the molecular basis of pancreatic cancer, substantial gaps remain in our understanding of disease pathogenesis and in the development of effective strategies for early diagnosis and treatment. With the completion of human genome sequencing in April 2003, it is possible to study and compare the human genome of a diseased tissue with that of its corresponding normal tissue in a single experiment. Toward this end, recent studies have used three global gene expression profile technologies to study pancreatic cancer: cDNA microarray [1,2,3,4,5], Affymetrix gene chip
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