Evidence map›Paper›PMID 24497320›Full record

ArticleHepatology (Baltimore, Md.)2014

Human bile contains microRNA-laden extracellular vesicles that can be used for cholangiocarcinoma diagnosis.

Ling Li, David Masica, Masaharu Ishida, Ciprian Tomuleasa, Sho Umegaki, Anthony N Kalloo, Christos Georgiades, Vikesh K Singh, Mouen Khashab, Stuart Amateau and 23 more

Erratum issuedAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 117 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 1 pooled it
9.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

117 citing papers in PubMed, 1 synthesis or guideline pooled it, 223 citations in OpenAlex.

  1. Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review.The American journal of tropical medicine and hygiene · 2018
    Pooled it
  2. Review
  3. Diagnostic and prognostic significance of circulating extracellular vesicles in gastrointestinal cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Cholangiocarcinoma: The era of liquid biopsy.World journal of gastroenterology · 2025
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Liquid Liver Biopsy for Disease Diagnosis and Prognosis.Journal of clinical and translational hepatology · 2023
    Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review

57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors at 9 institutions in 5 countries.

Ling LiDivision of Gastrenterology and Hepatology, Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland; USA.
David Masica
Masaharu Ishida
Ciprian Tomuleasa
Sho Umegaki
Anthony N Kalloo
Christos Georgiades
Vikesh K Singh
Mouen Khashab
Stuart Amateau
Zhiping Li
Patrick Okolo
Anne-Marie Lennon
Payal Saxena
Jean-Francois Geschwind
Todd Schlachter
Kelvin Hong
Timothy M Pawlik
Marcia Canto
Joanna Law
Reem Sharaiha
Clifford R Weiss
Paul Thuluvath
Michael Goggins
Eun Ji Shin
Haoran Peng
Vivek Kumbhari
Susan Hutfless
Liya Zhou
Esteban Mezey
Stephen J Meltzer
Rachel Karchin
Florin M Selaru
Beijing Hospital · CNJohns Hopkins University · USPeking University Third Hospital · CNAmerican Heart Institute · CYCornell University · USIuliu Hațieganu University of Medicine and Pharmacy · ROJohns Hopkins Hospital · USTohoku University · JPUniversity of Colorado Denver · US

Funding

SAN ANTONIO CENTER OF BIOMARKERS OF RISK FOR PROSTATE CAU01CA086402 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI LEACH, ROBIN JEAN, THOMPSON, IAN M. · 2000 to 2018
$33.1M
Translational Research Enhancement CoreP30DK089502 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK · 2011 to 2020
$12.0M
MicroRNA involvement in the regulation of biliary epitheliumK08DK090154 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI SELARU, FLORIN · 2011 to 2015
$706k
NCI NIH HHS U01 CA086402NIDDK NIH HHS K08 DK090154NIDDK NIH HHS K08 DK090154-01NIDDK NIH HHS P30 DK089502
6 · The paper itself

Abstract

unlabelledCholangiocarcinoma (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.

conclusionThese 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.

Indexed as

Bile Ducts, IntrahepaticAdultAgedAged, 80 and overBileBile Duct NeoplasmsBiomarkersCase-Control StudiesCholangiocarcinomaCytoplasmic VesiclesFemaleHumansMaleMicroRNAsMiddle AgedSupport Vector MachineBiomarkersMicroRNAs

Identifiers

PMID24497320
PMCPMC4121391
OpenAlexW2117651804

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.