NPTX2 hypermethylation in pure pancreatic juice predicts pancreatic neoplasms.
The neuronal pentraxin II (NPTX2) gene is methylated in over 90% primary pancreatic cancer tissues but rarely in normal pancreatic ductal epithelia. Here, the authors investigated the utility of methylated NPTX2 as a diagnostic marker for pancreatic cancer in pure pancreatic juice samples of patients with benign and malignant pancreatic diseases, including pancreatic cancer, intraductal papillary mucinous neoplasm or chronic pancreatitis using methylation-specific polymerase chain reaction (MSP) and quantitative MSP. MSP assays revealed that the incidence of aberrant NPTX methylation in pure pancreatic juice samples was 64.5% (20 of 31) in patients with pancreatic cancer, 70.0% (7 of 10) in patients with malignant intraductal papillary mucinous neoplasm, 33.3% (2 of 6) in patients with benign intraductal papillary mucinous neoplasm and 21.7% (5 of 23) in patients with chronic pancreatitis. NPTX2 hypermethylation in patients with chronic pancreatitis was significantly lower than that of pancreatic cancer (P < 0.01) or patients with intraductal papillary mucinous neoplasm (P < 0.05). At a cutoff value of 1.39 for quantitative MSP, the incidence of aberrant NPTX2 methylation was 61.3% (19 of 31) in patients with pancreatic cancer, 50.0% (5 of 10) in patients with malignant intraductal papillary mucinous neoplasm, 0% in patients with benign intraductal papillary mucinous neoplasm and 8.7% (2 of 23) in patients with chronic pancreatitis. There was a significant difference in NPTX2 methylation between pancreatic cancer and chronic pancreatitis (P < 0.01). Our findings indicate that detection of aberrant methylation of NPTX2 in pure pancreatic juice samples could be useful as a molecular marker to discriminate between patients with malignant and benign disease of the pancreas.
Departments of Breast Surgery, Research Unit of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China. yaofancmu@hotmail.com
Fan
F
Yao
Mingjun
M
Sun
Ming
M
Dong
Feng
F
Jing
Bo
B
Chen
Huimian
H
Xu
Shubao
S
Wang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002097:C-Reactive Protein / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010182:Pancreatic Diseases / Q000175:diagnosis / Q000235:genetics*; D010189:Pancreatic Juice / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D055815:Young Adult; D000099153:Pentraxins
D014408:Biomarkers, Tumor; D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D000099153:Pentraxins