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miR-21 in the Extracellular Vesicles (EVs) of Cerebrospinal Fluid (CSF): A Platform for Glioblastoma Biomarker Development

Open access
Akers, Johnny C., Ramakrishnan, Valya, Kim, Ryan, Skog, Johan, Nakano, Ichiro, Pingle, Sandeep, Kalinina, Juliya, Hua, Wei, Kesari, Santosh, Mao, Ying, Breakefield, Xandra O., Hochberg, Fred H., Van Meir, Erwin G., Carter, Bob S., Chen, Clark C.·2013·PLoS ONE

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.

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Metadata

Authors
Akers, J. C., Ramakrishnan, V., Kim, R., Skog, J., Nakano, I., Pingle, S., Kalinina, J., Hua, W., Kesari, S., Mao, Y., Breakefield, X. O., Hochberg, F. H., Van Meir, E. G., Carter, B. S., & Chen, C. C.
Venue
PLoS ONE
Published
2013-10-21
Volume
8
Issue
10
Pages
e78115
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2150309717
Cited by
337
References
14
FWCI
9.14
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: miR-21 in the Extracellular Vesicles (EVs) of Cerebrospinal Fluid (CSF): A Platform for Glioblastoma Biomarker Development. https://app.cochat.ai/papers/10.1371/journal.pone.0078115
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Akers, J. C., Ramakrishnan, V., Kim, R., Skog, J., Nakano, I., Pingle, S., Kalinina, J., Hua, W., Kesari, S., Mao, Y., Breakefield, X. O., Hochberg, F. H., Van Meir, E. G., Carter, B. S., & Chen, C. C. (2013). miR-21 in the Extracellular Vesicles (EVs) of Cerebrospinal Fluid (CSF): A Platform for Glioblastoma Biomarker Development. PLoS ONE. https://doi.org/10.1371/journal.pone.0078115

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.