RNA expression patterns in serum exosomes from patients with glioblastoma multiforme

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IWE – International Workshop on Exosomes — Paris (January 2011)
Authors: Mikkel Noerholm1,2, Tobias B. Limperg1,3, Leonora Balaj1, Afshin Salehi4, Fred H. Hochberg1, Bob Carter1,4, Lin Dan Zhu1, Xandra O. Breakefield1, Johan Skog1,2
Affiliations: 1Department of Neurology, Neurosurgery and Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA, USA; 2Exosome Diagnostics, New York, NY, USA; 3Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands; 4Division of Neurological Surgery, UCSD School of Medicine, San Diego, CA, USA

Microarray expression profiles of RNA isolated from serum exosomes/microvesicles (exoRNA) from glioblastoma (GBM) patients and normal healthy controls clearly separated the two groups when used in unsupervised clustering. This indicates distinct differences in the exoRNA from the two groups and highlights the potential diagnostic relevance of RNA contained in serum microvesicles. The most dominant expression dysregulation in GBM patients involved genes associated with ribosome production, which displayed highly significant downregulation in exoRNA from GBM patients, relative to normal control exoRNA. These genes (e.g. RPS12 and RPL11) have previously been shown to be upregulated in lymphocytes and the observed downregulation in serum exoRNA correlates well with lymphocytopenia also observed in these GBM patients. However, several genes were also observed to be upregulated in exoRNA from GBM patient serum, albeit with less significance and typically these genes were less differentially expressed. The RNA species showing differential expression by microarray were validated by qRT-PCR and normalized to stably expressed RNA species. This work is the first to report the ability to differentiate GBM patients from normal controls based on a gene expression blood test and the first to report differential expression analysis using RNA extracted from exosomes/microvesicles isolated from clinical serum samples.