RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls
Open accessAbstract
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.
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Tumor-derived EVs remain a small minority of total EVs in a biofluid sample, so sensitivity of detection remains a major challenge in tumor-specific biomarker development.
“Relative to this population, EVs derived from tumors remain a small minority of total EVs isolated in a given biofluid sample [118]. Thus, the sensitivity of detection remains a major challenge in tumor-specific biomarker development.”
From Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies (2013) · cites this paper as [118]
The Discussion says tumour-derived microvesicles in blood are likely to constitute a relatively small fraction of the total in many cases. The citing sentence presents this as categorical and extends it to biofluid samples generally; the cited paper's passage is qualified and concerns blood. The following sentence about detection sensitivity is the citing authors' inference, not a separately cited claim. (LLM, conf=0.86)
Experimental — accuracy not yet measuredmRNA profiling of serum-derived EV contents can discriminate between healthy and glioblastoma-bearing patients, and IDH-1, EGFRvIII, and c-myc alterations have been detected in EVs from glioblastoma or medulloblastoma samples.
“For example, mRNA profiling of serum derived EV contents can discriminate between healthy and glioblastoma bearing patients [118]. IDH-1 (isocitrate dehydrogenase 1) transcripts have been detected from EVs isolated from the blood of glioblastoma bearing patients using immunoisolations of EVs targeting CD63 [119].”
From Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies (2013) · cites this paper as [118]
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“This approach is based on previous reports from our laboratory and others (1, 5, 12, 13) and has been adapted for isolation of EV from cells in culture or from serum.”
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- Authors
- Noerholm, M., Balaj, L., Limperg, T., Salehi, A., Zhu, L. D., Hochberg, F. H., Breakefield, X. O., Carter, B. S., & Skog, J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Noerholm, Mikkel
- ORCID
- Venue
- BMC Cancer
- Published
- 2012-01-17
- Volume
- 12
- Issue
- 1
- Pages
- 22-22
- ISSN
- 1471-2407 (ISSN-L)
- PMC
- PMC3329625
- OpenAlex
- W2118369903
- Cited by
- 190
- References
- 42
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 13 · 2020: 10 · 2019: 16 · 2018: 18 · 2017: 12 · 2016: 17 · 2015: 20 · 2014: 28 · 2013: 25 · 2012: 6
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Cancer (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute (R21CA156009, P01CA069246, CA069246, CA156009, R21CA141226, CA141226)
- National Institute of Neurological Disorders and Stroke (P30NS045776)
- National Center for Research Resources (UL1RR025758)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- glioblastoma, exosomes, tumour biomarkers, ribosomal proteins, ribosome biogenesis, gene expression profiling, differential gene expression, liquid biopsy
- MeSH terms
- Brain Neoplasms, Glioblastoma, Humans, RNA, Neoplasm, Subcellular Fractions, Biomarkers, Tumor, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Microarray Analysis
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