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Open Access Highly Accessed Research article

RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls

Mikkel Noerholm12*, Leonora Balaj1, Tobias Limperg13, Afshin Salehi14, Lin Dan Zhu1, Fred H Hochberg1, Xandra O Breakefield1, Bob S Carter14 and Johan Skog12

Author Affiliations

1 Department of Neurology, Neurosurgery and Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA

2 Exosome Diagnostics, Inc., Lasker Biomedical Research Building, Columbia University Medical Center, 3960 Broadway, Suite 540, New York, NY 10032, USA

3 Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands

4 Division of Neurological Surgery, UCSD School of Medicine, San Diego, CA 92103, USA

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BMC Cancer 2012, 12:22  doi:10.1186/1471-2407-12-22

Published: 17 January 2012

Abstract

Background

RNA from exosomes and other microvesicles contain transcripts of tumour origin. In this study we sought to identify biomarkers of glioblastoma multiforme in microvesicle RNA from serum of affected patients.

Methods

Microvesicle RNA from serum from patients with de-novo primary glioblastoma multiforme (N = 9) and normal controls (N = 7) were analyzed by microarray analysis. Samples were collected according to protocols approved by the Institutional Review Board. Differential expressions were validated by qRT-PCR in a separate set of samples (N = 10 in both groups).

Results

Expression profiles of microvesicle RNA correctly separated individuals in two groups by unsupervised clustering. The most significant differences pertained to down-regulated genes (121 genes > 2-fold down) in the glioblastoma multiforme patient microvesicle RNA, validated by qRT-PCR on several genes. Overall, yields of microvesicle RNA from patients was higher than from normal controls, but the additional RNA was primarily of size < 500 nt. Gene ontology of the down-regulated genes indicated these are coding for ribosomal proteins and genes related to ribosome production.

Conclusions

Serum microvesicle RNA from patients with glioblastoma multiforme has significantly down-regulated levels of RNAs coding for ribosome production, compared to normal healthy controls, but a large overabundance of RNA of unknown origin with size < 500 nt.

Keywords:
Exosomes; Microvesicles; Microarray; Biomarkers; Serum; Glioma