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Human bile contains microRNA-laden extracellular vesicles that can be used for
cholangiocarcinoma diagnosis
#MMPMID24497320
Li L
; Masica D
; Ishida M
; Tomuleasa C
; Umegaki S
; Kalloo AN
; Georgiades C
; Singh VK
; Khashab M
; Amateau S
; Li Z
; Okolo P
; Lennon AM
; Saxena P
; Geschwind JF
; Schlachter T
; Hong K
; Pawlik TM
; Canto M
; Law J
; Sharaiha R
; Weiss CR
; Thuluvath P
; Goggins M
; Shin EJ
; Peng H
; Kumbhari V
; Hutfless S
; Zhou L
; Mezey E
; Meltzer SJ
; Karchin R
; Selaru FM
Hepatology
2014[Sep]; 60
(3
): 896-907
PMID24497320
show ga
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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