TY - JOUR
T1 - Human bile contains MicroRNA-laden extracellular vesicles that can be used for cholangiocarcinoma diagnosis
AU - Li, Ling
AU - Masica, David
AU - Ishida, Masaharu
AU - Tomuleasa, Ciprian
AU - Umegaki, Sho
AU - Kalloo, Anthony N.
AU - Georgiades, Christos
AU - Singh, Vikesh K.
AU - Khashab, Mouen
AU - Amateau, Stuart
AU - Li, Zhiping
AU - Okolo, Patrick
AU - Lennon, Anne Marie
AU - Saxena, Payal
AU - Geschwind, Jean Francois
AU - Schlachter, Todd
AU - Hong, Kelvin
AU - Pawlik, Timothy M.
AU - Canto, Marcia
AU - Law, Joanna
AU - Sharaiha, Reem
AU - Weiss, Clifford R.
AU - Thuluvath, Paul
AU - Goggins, Michael
AU - Shin, Eun Ji
AU - Peng, Haoran
AU - Kumbhari, Vivek
AU - Hutfless, Susan
AU - Zhou, Liya
AU - Mezey, Esteban
AU - Meltzer, Stephen J.
AU - Karchin, Rachel
AU - Selaru, Florin M.
PY - 2014/9
Y1 - 2014/9
N2 - Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary sclerosing cholangitis (PSC) patients pose a particularly difficult clinical dilemma because they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers, and size distribution of human biliary EVs. Utilizing multivariate organization of combinatorial alterations (MOCA), we defined a novel biliary vesicle miR-based panel for CCA diagnosis that demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. Conclusion: These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR-based disease markers in bile. Finally, we report on the development of a novel bile-based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility.
AB - Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary sclerosing cholangitis (PSC) patients pose a particularly difficult clinical dilemma because they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers, and size distribution of human biliary EVs. Utilizing multivariate organization of combinatorial alterations (MOCA), we defined a novel biliary vesicle miR-based panel for CCA diagnosis that demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. Conclusion: These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR-based disease markers in bile. Finally, we report on the development of a novel bile-based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility.
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U2 - 10.1002/hep.27050
DO - 10.1002/hep.27050
M3 - Article
C2 - 24497320
AN - SCOPUS:84906794646
SN - 0270-9139
VL - 60
SP - 896
EP - 907
JO - Hepatology
JF - Hepatology
IS - 3
ER -