Abstract
The increasing interest in identifying molecular biomarkers to determine patient prognosis in glioblastoma multiforme (GBM) has resulted in several microRNA (miRNA)-based signatures able to predict progression-free and overall survival. However, the coherency between these signatures is small, and correlations to clinicopathological features other than survival are seldom seen. The aim of this study was to identify any significant relationship between miRNA signatures and clinicopathological data by combining pathological features with miRNA and mRNA analysis in fourteen GBM patients. In total, 161 miRNAs were shown to cluster the GBM tumor samples into long- and short-term-surviving patients. Many of these miRNAs were associated with differential expression in GBM, including a number of miRNAs shown to confer risk or protection with respect to clinical outcome and to modulate the mesenchymal mode of migration and invasion. An inverse relationship between miR-125b and nestin expression was identified and correlated with overall survival in GBM patients, eloquently illustrating how clinicopathological findings and molecular profiling may be a relevant combination to predict patient outcome. The intriguing finding that many of the differentially expressed miRNAs contained exosome-packaging motifs in their mature sequences suggests that we must expand our view to encompass the complex intercellular communication in order to identify molecular prognostic biomarkers and to increase our knowledge in the field of GBM pathogenesis.
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Abbreviations
- 3′UTR:
-
3′ Untranslated region
- 5ALA:
-
5-Aminolevulinic acid
- CNS:
-
Central nervous system
- EGFR:
-
Epidermal growth factor receptor
- EXO-motif:
-
Exosome-packaging-associated motif
- GBM:
-
Glioblastoma multiforme
- GFAP:
-
Glial fibrillary acidic protein
- IDH1:
-
Isocitrate dehydrogenase 1
- MAD:
-
Median absolute deviation
- MGMT:
-
Methyl guanine methyl transferase
- miRNA:
-
MicroRNA
- MMMI:
-
Mesenchymal mode of migration and invasion
- mRNA:
-
Messenger RNA
- RNA:
-
Ribonucleic acid
- TCGA:
-
The Cancer Genome Atlas
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Acknowledgments
The authors would like to acknowledge laboratory technician Rikke Sophie Holm Kristensen, Aalborg University for her excellent technical assistance. Sille Jensen, Julie Vedel, Spogmai Zadran, Ditte Hansen and Line Tegtmeier Frandsen are acknowledged for their help in gathering the clinical data. This work was supported by grants from Det Obelske Familiefond and Spar Nord Fonden. Kasper Bendix Johnsen is supported by the Novo Scholarship Programme (Novo Nordisk, Denmark).
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Henriksen, M., Johnsen, K.B., Olesen, P. et al. MicroRNA Expression Signatures and Their Correlation with Clinicopathological Features in Glioblastoma Multiforme. Neuromol Med 16, 565–577 (2014). https://doi.org/10.1007/s12017-014-8309-7
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DOI: https://doi.org/10.1007/s12017-014-8309-7