Evidence map›Paper›PMID 24205116›Full record

ArticlePloS one2013

MiR-21 in the extracellular vesicles (EVs) of cerebrospinal fluid (CSF): a platform for glioblastoma biomarker development.

Johnny C Akers, Valya Ramakrishnan, Ryan Kim, Johan Skog, Ichiro Nakano, Sandeep Pingle, Juliya Kalinina, Wei Hua, Santosh Kesari, Ying Mao and 5 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 234 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
234citing papers in PubMed, 5 pooled it
10.0field-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

234 citing papers in PubMed, 5 syntheses or guidelines pooled it, 326 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Review
  7. Review
  8. Article
  9. Review
  10. Transcriptomic and functional analysis of fibroid extracellular vesicles.Clinical science (London, England : 1979) · 2026
    Article
  11. Review
  12. Article
  13. Review
  14. Exosome-like Nanovesicles fromMolecules (Basel, Switzerland) · 2026
    Article
  15. Article
  16. Review
  17. Extracellular RNAs as Messengers and Early Biomarkers in Neurodegeneration.International journal of molecular sciences · 2025
    Review
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 9 institutions in 2 countries.

Johnny C AkersCenter for Theoretical and Applied Neuro-Oncology, University of California, San Diego, California, United States of America.
Valya Ramakrishnan
Ryan Kim
Johan Skog
Ichiro Nakano
Sandeep Pingle
Juliya Kalinina
Wei Hua
Santosh Kesari
Ying Mao
Xandra O Breakefield
Fred H Hochberg
Erwin G Van Meir
Bob S Carter
Clark C Chen
University of California, San Diego · USCenter for Theoretical Biological Physics · USFudan University · CNEmory University · USExosome Diagnostics (United States) · USHarvard University · USMassachusetts General Hospital · USThe Ohio State University · USWinship Cancer Institute

Funding

The role of microvesicles in giloma virotherapyP01CA069246 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CHAREST, ALAIN · 1996 to 2021
$30.9M
exRNA Biomarkers for Human GliomaUH3TR000931 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CARTER, BOB S, HOCHBERG, FRED H · 2015 to 2017
$3.0M
Defining mechanisms of extracellular communication for cancer therapyR01CA163722 · NCI · EMORY UNIVERSITY · PI VAN MEIR, ERWIN G. · 2013 to 2017
$1.7M
exRNA Biomarkers for Human GliomaUH2TR000931 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CARTER, BOB S, HOCHBERG, FRED H · 2013 to 2014
$1.1M
NCATS NIH HHS UH2 TR000931NCATS NIH HHS UH3 TR000931NCI NIH HHS P01 CA069246NCI NIH HHS R01 CA163722
6 · The paper itself

Abstract

Glioblastoma cells secrete extra-cellular vesicles (EVs) containing microRNAs (miRNAs). Analysis of these EV miRNAs in the bio-fluids of afflicted patients represents a potential platform for biomarker development. However, the analytic algorithm for quantitative assessment of EV miRNA remains under-developed. Here, we demonstrate that the reference transcripts commonly used for quantitative PCR (including GAPDH, 18S rRNA, and hsa-miR-103) were unreliable for assessing EV miRNA. In this context, we quantitated EV miRNA in absolute terms and normalized this value to the input EV number. Using this method, we examined the abundance of miR-21, a highly over-expressed miRNA in glioblastomas, in EVs. In a panel of glioblastoma cell lines, the cellular levels of miR-21 correlated with EV miR-21 levels (p<0.05), suggesting that glioblastoma cells actively secrete EVs containing miR-21. Consistent with this hypothesis, the CSF EV miR-21 levels of glioblastoma patients (n=13) were, on average, ten-fold higher than levels in EVs isolated from the CSF of non-oncologic patients (n=13, p<0.001). Notably, none of the glioblastoma CSF harbored EV miR-21 level below 0.25 copies per EV in this cohort. Using this cut-off value, we were able to prospectively distinguish CSF derived from glioblastoma and non-oncologic patients in an independent cohort of twenty-nine patients (Sensitivity=87%; Specificity=93%; AUC=0.91, p<0.01). Our results suggest that CSF EV miRNA analysis of miR-21 may serve as a platform for glioblastoma biomarker development.

Indexed as

Biomarkers, TumorCell Line, TumorCerebrospinal FluidGlioblastomaHumansMicroRNAsReverse Transcriptase Polymerase Chain ReactionRNA, Ribosomal, 18SBiomarkers, TumorMicroRNAsMIRN103 microRNA, humanMIRN21 microRNA, humanRNA, Ribosomal, 18S

Identifiers

PMID24205116
PMCPMC3804457
OpenAlexW2150309717

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.