Analysis of U2 small nuclear RNA fragments in the bile differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders.
OBJECTIVE
Up to now the diagnosis of early stage cholangiocarcinoma (CC) has remained difficult, with low sensitivities reported for current diagnostic methods. Based on recent promising findings about circulating U2 small nuclear RNA fragments (RNU2-1f) as novel blood-based biomarkers for pancreatic and colorectal adenocarcinoma, we studied the utility of RNU2-1f as a diagnostic marker of CC in bile fluid.


METHODS
Bile fluid was collected from patients with CC (n = 12), controls (patients with choledocholithiasis) (n = 11) and with primary sclerosing cholangitis (PSC; n = 11). RNU2-1f levels were measured by real-time polymerase chain reaction normalized to cel-54.


RESULTS
Measurement of RNU2-1f levels in bile fluids enabled the differentiation of patients with CC from controls in all cases. Furthermore, RNU2-1f levels in bile fluids of patients with CC were significantly higher than in patients with PSC, resulting in a receiver-operating characteristic curve area of 0.856, with sensitivity of 67 % and specificity of 91 %.


CONCLUSIONS
Our data suggest that the measurement of RNU2-1 fragments detected in the bile fluid can be used as a diagnostic marker for CC and should be included in future prospective diagnostic studies for this disease entity.
Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany, alexander.baraniskin@rub.de.
Alexander
A
Baraniskin
Stefanie
S
Nöpel-Dünnebacke
Brigitte
B
Schumacher
Christian
C
Gerges
Thilo
T
Bracht
Barbara
B
Sitek
Helmut E
HE
Meyer
Guido
G
Gerken
Alexander
A
Dechene
Jörg F
JF
Schlaak
Roland
R
Schroers
Christian
C
Pox
Wolff
W
Schmiegel
Stephan A
SA
Hahn
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001646:Bile / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D015209:Cholangitis, Sclerosing / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D010865:Pilot Projects; D012342:RNA, Small Nuclear / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000378:metabolism*; D012680:Sensitivity and Specificity
D015415:Biomarkers; D010446:Peptide Fragments; D012342:RNA, Small Nuclear; D017413:Ribonucleoprotein, U2 Small Nuclear; C405484:U2 small nuclear RNA