Quantitative analysis of NPTX2 hypermethylation is a promising molecular diagnostic marker for pancreatic cancer.
OBJECTIVE
Percutaneous fine-needle aspiration cytology or biopsy has been used for pathological confirmation in pancreatic cancer. Sometimes, it is difficult to approach the mass because of surrounding major vessels, and there is a risk of seeding. Although endoscopic retrograde cholangiopancreatography (ERCP)-guided pancreatic duct brush cytology is less invasive, its reliability is very low. Recently, aberrantly methylated genes were reported in pancreatic cancer tissue. This study was to develop a novel molecular diagnostic approach based on epigenetic characteristics.


METHODS
We enrolled pathologically proven 33 pancreatic cancer patients and 22 benign pancreaticobiliary disease patients. The ERCP-guided pancreatic duct brush cytology samples were obtained. Genomic DNA was extracted, and NPTX2 CpG island hypermethylation was examined quantitatively by real-time polymerase chain reaction amplification after chemical modification.


RESULTS
Pancreatic cancer cytology samples had statistically significant higher levels of NPTX2 methylation compared with benign diseases, and the optimal cutoff value of NPTX2 methylation was 1.2%. The sensitivity was 87%, and specificity was 80%, whereas pathological examination by ERCP-guided pancreatic duct brush cytology had a sensitivity of 38%.


CONCLUSIONS
The quantitative analysis of NPTX2 hypermethylation may play a role in making highly sensitive and less invasive diagnosis of pancreatic cancer. Therefore, NPTX2 hypermethylation could be a promising molecular diagnostic marker.
Park
Joo Kyung
JK
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Ryu
Ji Kon
JK
Lee
Kwang Hyuk
KH
Lee
Jun Kyu
JK
Yoon
Won Jae
WJ
Lee
Sang Hyub
SH
Yoo
Ji Won
JW
Woo
Sang Myung
SM
Lee
Gyung Yub
GY
Lee
Cheol Ho
CH
Kim
Yong-Tae
YT
Yoon
Yong Bum
YB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002097:C-Reactive Protein / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000175:diagnosis*; D002760:Cholangiopancreatography, Endoscopic Retrograde; D003199:Computer Systems; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis* / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010182:Pancreatic Diseases / Q000175:diagnosis / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000175:diagnosis*; D016133:Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D000099153:Pentraxins
D014408:Biomarkers, Tumor; D002097:C-Reactive Protein; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D000099153:Pentraxins