Elevated level of anterior gradient-2 in pancreatic juice from patients with pre-malignant pancreatic neoplasia.
BACKGROUND
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.


RESULTS
Twenty 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 < or = 0.03). By ROC analysis, the AGR2 ELISA achieved 67% sensitivity at 90% specificity in predicting PanIN3 juice samples from the benign disease controls.


CONCLUSIONS
These 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.
Chen
Ru
R
GI Division/Department of Medicine, University of Washington, Seattle, WA 98195 USA. ruc@medicine.washington.edu
Pan
Sheng
S
Duan
Xiaobo
X
Nelson
Brad H
BH
Sahota
Rob A
RA
de Rham
Sarah
S
Kozarek
Richard A
RA
McIntosh
Martin
M
Brentnall
Teresa A
TA
D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002278:Carcinoma in Situ / Q000378:metabolism*; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D009088:Mucoproteins; D015513:Oncogene Proteins; D010189:Pancreatic Juice / Q000737:chemistry / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism*; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics; D012372:ROC Curve; D055815:Young Adult
C502296:AGR2 protein, human; D014408:Biomarkers, Tumor; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins