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Abstract
BackgroundPancreatic intraepithelial neoplasias (PanINs) are precursors of malignant pancreatic cancer, an ideal stage for early cancer detection. We applied quantitative proteomics to identify aberrantly elevated proteins in pancreatic juice samples derived from patients with PanIN3.ResultsTwenty proteins were found elevated in all three PanIN juices by at least two-fold. Among these proteins, anterior gradient-2 (AGR2) was found to be 2-10 fold elevated in PanIN3 juice samples analyzed by quantitative proteomics. An ELISA assay was developed to evaluate AGR2 levels in 51 pancreatic juice samples and 23 serum samples from patients with pancreatic cancer, pre-malignant lesions (including PanIN3, PanIN2, Intraductal Papillary Mucinous Neoplasms (IPMNs)) and benign disease controls (including chronic pancreatitis). AGR2 levels in the pancreatic juice samples were found significantly elevated in patients with pre-malignant conditions (PanINs and IPMNs) as well as pancreatic cancer compared to control samples (p ≤ 0.03). By ROC analysis, the AGR2 ELISA achieved 67% sensitivity at 90% specificity in predicting PanIN3 juice samples from the benign disease controls.ConclusionsThese results suggest that elevation of AGR2 levels in pancreatic juice occurs in early pancreatic cancer progression and could be further investigated as a potential candidate juice biomarker for early detection of pancreatic cancer.
Highlights
Pancreatic cancer is the fourth leading cause of cancer death in the United States [1]
Identification of elevated proteins in pancreatic juice samples from patients with PanIN3 by quantitative proteomics Quantitative proteomics analysis using stable isotope labeling and tandem mass spectrometry was applied to identify proteins abnormally elevated in the pancreatic juice samples from PanIN3 patients
We identified twenty proteins displaying elevated levels by at least two-fold in all three PanIN3 juices when compared to normal control juice (Table 2)
Summary
Pancreatic cancer is the fourth leading cause of cancer death in the United States [1]. The poor prognosis could potentially be improved by development of biomarkers that could be used for early detection. Pancreatic intraepithelial neoplasia or PanIN, represents the precursor lesion for pancreatic ductal adenocarcinoma and is graded 1-3, with PanIN3 representing the stage just before cancer. Advanced PanIN lesions, e.g. PanIN3, would be an ideal stage to diagnose patients, as this represents a time point when intervention and cure is possible. Pancreatic juice is a proximal body fluid and represents an opportune specimen for identifying biomarkers of pancreatic cancer. Pancreatic intraepithelial neoplasias (PanINs) are precursors of malignant pancreatic cancer, an ideal stage for early cancer detection. We applied quantitative proteomics to identify aberrantly elevated proteins in pancreatic juice samples derived from patients with PanIN3
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