TY - JOUR
T1 - A pilot study to develop a diagnostic test for pancreatic ductal adenocarcinoma based on differential expression of select miRNA in plasma and bile
AU - Cote, Gregory A.
AU - Gore, A. Jesse
AU - McElyea, Samantha D.
AU - Heathers, Laura E.
AU - Xu, Huiping
AU - Sherman, Stuart
AU - Korc, Murray
N1 - Publisher Copyright:
© 2014 by the American College of Gastroenterology.
PY - 2014/12/11
Y1 - 2014/12/11
N2 - OBJECTIVES:Accurate peripheral markers for the diagnosis of pancreatic ductal adenocarcinoma (PDAC) are lacking. We measured the differential expression of select microRNAs (miRNAs) in plasma and bile among patients with PDAC, chronic pancreatitis (CP), and controls.METHODS:We identified patients (n=215) with treatment-naive PDAC (n=77), CP with bile/pancreatic duct pathology (n=67), and controls (n=71) who had been prospectively enrolled in a Pancreatobiliary Biorepository at the time of endoscopic retrograde cholangiopancreatography or endoscopic ultrasound. Controls were patients with choledocholithiasis but normal pancreata. The sample was separated into training (n=95) and validation (n=120) cohorts to establish and then test the performance of PDAC Signature Panels in diagnosing PDAC. The training cohort (n=95) included age-matched patients with PDAC, CP, and controls. Panels were derived from the differential expression of 10 candidate miRNAs in plasma or bile. We selected miRNAs having excellent accuracy for inclusion in regression models.RESULTS:Using the training cohort, we confirmed the differential expression of 9/10 miRNAs in plasma (miR-10b,-30c,-106b,-132,-155,-181a,-181b,-196a, and-212) and 7/10 in bile (excluding miR-21,-132, and-181b). Of these, five (miR-10b,-155,-106b,-30c, and-212) had excellent accuracy for distinguishing PDAC. In the training and validation cohorts, the sensitivity/specificity for a PDAC Panel derived from plasma was 95/100% and 100/100%, respectively; in bile, these were 96/100% and 100/100%.CONCLUSIONS:Increased expression of miRNA-10b,-155, and-106b in plasma appears highly accurate in diagnosing PDAC. Additional studies are needed to confirm this Panel and explore its value as a prognostic test.
AB - OBJECTIVES:Accurate peripheral markers for the diagnosis of pancreatic ductal adenocarcinoma (PDAC) are lacking. We measured the differential expression of select microRNAs (miRNAs) in plasma and bile among patients with PDAC, chronic pancreatitis (CP), and controls.METHODS:We identified patients (n=215) with treatment-naive PDAC (n=77), CP with bile/pancreatic duct pathology (n=67), and controls (n=71) who had been prospectively enrolled in a Pancreatobiliary Biorepository at the time of endoscopic retrograde cholangiopancreatography or endoscopic ultrasound. Controls were patients with choledocholithiasis but normal pancreata. The sample was separated into training (n=95) and validation (n=120) cohorts to establish and then test the performance of PDAC Signature Panels in diagnosing PDAC. The training cohort (n=95) included age-matched patients with PDAC, CP, and controls. Panels were derived from the differential expression of 10 candidate miRNAs in plasma or bile. We selected miRNAs having excellent accuracy for inclusion in regression models.RESULTS:Using the training cohort, we confirmed the differential expression of 9/10 miRNAs in plasma (miR-10b,-30c,-106b,-132,-155,-181a,-181b,-196a, and-212) and 7/10 in bile (excluding miR-21,-132, and-181b). Of these, five (miR-10b,-155,-106b,-30c, and-212) had excellent accuracy for distinguishing PDAC. In the training and validation cohorts, the sensitivity/specificity for a PDAC Panel derived from plasma was 95/100% and 100/100%, respectively; in bile, these were 96/100% and 100/100%.CONCLUSIONS:Increased expression of miRNA-10b,-155, and-106b in plasma appears highly accurate in diagnosing PDAC. Additional studies are needed to confirm this Panel and explore its value as a prognostic test.
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U2 - 10.1038/ajg.2014.331
DO - 10.1038/ajg.2014.331
M3 - Article
C2 - 25350767
AN - SCOPUS:84927177778
SN - 0002-9270
VL - 109
SP - 1942
EP - 1952
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
IS - 12
ER -