BI-11 PROGNOSTIC microRNAS IN MALIGNANT GLIOMA

MicroRNAs are short non-coding RNAs that act as micro-managers of cellular function. Their dysregulation is well documented in many cancers. TCGA microRNA expression data is available to identify the prognostic potential of microRNAs in malignant glioma. Using the LASSO statistical approach for 475...

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Bibliographic Details
Published in:Neuro-oncology (Charlottesville, Va.) Va.), 2014-11, Vol.16 (suppl 5), p.v25-v25
Main Authors: Hayes, J., Thygesen, H., Droop, A., Boissinot, M., Bellamy, C., Hughes, T., Westhead, D., Shaw, L., Wurdak, H., Lawler, S., Short, S.
Format: Article
Language:English
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Summary:MicroRNAs are short non-coding RNAs that act as micro-managers of cellular function. Their dysregulation is well documented in many cancers. TCGA microRNA expression data is available to identify the prognostic potential of microRNAs in malignant glioma. Using the LASSO statistical approach for 475 glioblastomas in the TCGA dataset we identified a nine-microRNA signature that predicts overall (p = 2.26e-09) and progression-free survival (p = 9.91e-08) with superior power than conventional molecular markers, including MGMT methylation status. This signature has significance in all molecular subtypes of glioblastoma with the exception of the non-G-CIMP proneural group and validated in a separate validation cohort (p = 4.50E-02). The signature also predicts survival in grade II and III disease (p = 5.20e-03). The great majority of microRNAs in the signature have previously been shown to play a role in glioma biology. In addition, when we compared patient groups at the extremes of survival in grade III astrocytoma (poor prognosis n = 10, survival 48 months) and glioblastoma (poor prognosis n = 14, survival 48 months), we found that microRNA profiles aligned with specific neuro-developmental pathways were associated with outcomes. Specifically, poorer prognosis disease was associated with profiles aligned towards glial-restricted and oligodendrocyte precursor (OP) cells. Furthermore, correlation of microRNA expression patterns of OPs with expression of 39 grade III astrocytomas and 558 glioblastomas predicts survival with high significance (p= 5.50e-06), indicating that the more tightly a grade III or IV tumor correlates with an OP profile, the poorer the outcome. These observations indicate that microRNAs have predictive power in malignant glioma. MicroRNA expression patterns may also reveal important aspects of underlying tumor biology. This data, coupled with the superior stability of microRNAs over mRNAs in clinical specimens, suggests they may represent attractive candidates as novel biomarkers for the disease.
ISSN:1522-8517
1523-5866
DOI:10.1093/neuonc/nou239.11