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BMC Cancer. 2012; 12: 22.
Published online Jan 17, 2012. doi:  10.1186/1471-2407-12-22
PMCID: PMC3329625
RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls
Mikkel Noerholm,corresponding author1,2 Leonora Balaj,1 Tobias Limperg,1,3 Afshin Salehi,1,4 Lin Dan Zhu,1 Fred H Hochberg,1 Xandra O Breakefield,1 Bob S Carter,1,4 and Johan Skog1,2
1Department of Neurology, Neurosurgery and Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA
2Exosome Diagnostics, Inc., Lasker Biomedical Research Building, Columbia University Medical Center, 3960 Broadway, Suite 540, New York, NY 10032, USA
3Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
4Division of Neurological Surgery, UCSD School of Medicine, San Diego, CA 92103, USA
corresponding authorCorresponding author.
Mikkel Noerholm: mikkel/at/exosomedx.com; Leonora Balaj: Balaj.Leonora/at/mgh.harvard.edu; Tobias Limperg: tobiaslimperg/at/gmail.com; Afshin Salehi: afsalehimd/at/gmail.com; Lin Dan Zhu: ldzhu/at/partners.org; Fred H Hochberg: fhochberg/at/partners.org; Xandra O Breakefield: breakefield/at/hms.harvard.edu; Bob S Carter: bobcarter/at/ucsd.edu; Johan Skog: johan/at/exosomedx.com
Received October 30, 2011; Accepted January 17, 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
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