PMID- 24205116
OWN - NLM
STAT- MEDLINE
DCOM- 20140918
LR  - 20240326
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 10
DP  - 2013
TI  - MiR-21 in the extracellular vesicles (EVs) of cerebrospinal fluid (CSF): a 
      platform for glioblastoma biomarker development.
PG  - e78115
LID - 10.1371/journal.pone.0078115 [doi]
LID - e78115
AB  - 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.
FAU - Akers, Johnny C
AU  - Akers JC
AD  - Center for Theoretical and Applied Neuro-Oncology, University of California, San 
      Diego, California, United States of America.
FAU - Ramakrishnan, Valya
AU  - Ramakrishnan V
FAU - Kim, Ryan
AU  - Kim R
FAU - Skog, Johan
AU  - Skog J
FAU - Nakano, Ichiro
AU  - Nakano I
FAU - Pingle, Sandeep
AU  - Pingle S
FAU - Kalinina, Juliya
AU  - Kalinina J
FAU - Hua, Wei
AU  - Hua W
FAU - Kesari, Santosh
AU  - Kesari S
FAU - Mao, Ying
AU  - Mao Y
FAU - Breakefield, Xandra O
AU  - Breakefield XO
FAU - Hochberg, Fred H
AU  - Hochberg FH
FAU - Van Meir, Erwin G
AU  - Van Meir EG
FAU - Carter, Bob S
AU  - Carter BS
FAU - Chen, Clark C
AU  - Chen CC
LA  - eng
GR  - P01 CA069246/CA/NCI NIH HHS/United States
GR  - R01 CA163722/CA/NCI NIH HHS/United States
GR  - UH2 TR000931/TR/NCATS NIH HHS/United States
GR  - UH3 TR000931/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131021
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (MIRN103 microRNA, human)
RN  - 0 (MIRN21 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Ribosomal, 18S)
SB  - IM
MH  - Biomarkers, Tumor/*cerebrospinal fluid
MH  - Cell Line, Tumor
MH  - Cerebrospinal Fluid/*metabolism
MH  - Glioblastoma/*genetics
MH  - Humans
MH  - MicroRNAs/*genetics
MH  - RNA, Ribosomal, 18S/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC3804457
COIS- Competing Interests: We would like to declare that one of the co-author, Johan 
      Skog, is an employee at Exosome Diagnostics. No other authors have any competing 
      interests. This does not alter our adherence to all the PLOS ONE policies on 
      sharing data and materials.
EDAT- 2013/11/10 06:00
MHDA- 2014/09/19 06:00
PMCR- 2013/10/21
CRDT- 2013/11/09 06:00
PHST- 2013/05/08 00:00 [received]
PHST- 2013/09/09 00:00 [accepted]
PHST- 2013/11/09 06:00 [entrez]
PHST- 2013/11/10 06:00 [pubmed]
PHST- 2014/09/19 06:00 [medline]
PHST- 2013/10/21 00:00 [pmc-release]
AID - PONE-D-13-18843 [pii]
AID - 10.1371/journal.pone.0078115 [doi]
PST - epublish
SO  - PLoS One. 2013 Oct 21;8(10):e78115. doi: 10.1371/journal.pone.0078115. 
      eCollection 2013.