Accurate discrimination of pancreatic ductal adenocarcinoma and chronic pancreatitis using multimarker expression data and samples obtained by minimally invasive fine needle aspiration.
To augment cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC) in tissue samples obtained by minimally invasive endoscopic ultrasound-guided fine needle aspiration, we investigated whether a small set of molecular markers could accurately distinguish PDAC from chronic pancreatitis (CP). Expression levels of 29 genes were first determined by quantitative real-time RT-PCR in a training set of tissues in which the final diagnosis was PDAC (n=20) or CP (n=10). Using receiver operator characteristic curve analysis, we determined that the single gene with the highest diagnostic accuracy for discrimination of CP vs. PDAC in the training study was urokinase plasminogen activator receptor (UPAR; AUC value = 0.895, 95% CI=0.728-0.976). In the set of test tissues (n=14), the accuracy of UPAR decreased to 79%. However, we observed that the addition of 6 genes (EPCAM2, MAL2, CEA5, CEA6, MSLN and TRIM29; referred to as the 6-gene classifier) to UPAR resulted in high accuracy in both training and testing sets. Excluding 3 samples (out of 44; 7%) for which results of the UPAR/6-gene classifier were "undefined," the accuracy of the UPAR/6-gene classifier was 100% in training samples (n=29), 92% in 12 test samples (p=0.004 that results were randomly generated; p=0.046 that the UPAR/6-gene classifier was comparable to UPAR alone; chi2 test), 100% in 3 samples for which the initial cytological diagnosis was "suspicious" and 98% (40/41) overall. Our results provide evidence that molecular marker expression data can be used to augment cytological analysis.
Chen
Yian
Y
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Zheng
Bin
B
Robbins
David H
DH
Lewin
David N
DN
Mikhitarian
Kaidi
K
Graham
Amanda
A
Rumpp
Laurrie
L
Glenn
Tammy
T
Gillanders
William E
WE
Cole
David J
DJ
Lu
Xinghua
X
Hoffman
Brenda J
BJ
Mitas
Michael
M
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D044963:Biopsy, Fine-Needle; D002272:Carcinoembryonic Antigen / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D000090204:Mesothelin; D008875:Middle Aged; D019060:Minimally Invasive Surgical Procedures; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009363:Neoplasm Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics; D050500:Pancreatitis, Chronic / Q000175:diagnosis*; D011379:Prognosis; D011510:Proteolipids / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000235:genetics
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D058851:GPI-Linked Proteins; C438606:MAL2 protein, human; C000715527:MSLN protein, human; D008562:Membrane Glycoproteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009363:Neoplasm Proteins; C524898:PLAUR protein, human; D011510:Proteolipids; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C087296:TRIM29 protein, human; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D000090204:Mesothelin