PURPOSE: MicroRNAs (miRNA) are short non-coding RNAs that can play critical roles in diverse biological processes. They are implicated in tumorigenesis and function as both tumor suppressors and oncogenes. The clinical significance of miRNA expression profiles in malignant gliomas remains unclear. EXPERMENTAL DESIGN: In this study, we examined the expression levels of 365 mature human miRNAs in 12 malignant gliomas, including 8 glioblastomas (GBMs) and 4 anaplastic astrocytomas (AAs), using TaqMan real-time quantitative PCR arrays. A validation study was performed to corroborate a subset of the results, including expression levels of miR-196a, 196b, 21, and 15b, by analyzing 92 malignant gliomas by conventional real time PCR. We modeled the relationship between the expression levels of these miRNAs and the survival rate of 39 GBM patients by Kaplan-Meier method and multivariate analysis. RESULTS: Expression profiles in GBMs and AAs suggested that 16 miRNAs were candidate markers associated with the malignant progression of gliomas. Among them, miR-196a showed the most significant difference (p=0.0038) and miR-196b also had a high significance (p=0.0371). Both miRNAs showed increased expression levels in GBMs relative to both AAs and normal brains in the validation study. Furthermore, patients with high miR-196 expression levels showed significantly poorer survival by the Kaplan-Meier method (p=0.0073). Multivariate analysis demonstrated that miR-196 expression levels were an independent predictor of overall survival in all 39 GBM patients (p=0.021, HR=2.81). CONCLUSIONS: Our results suggest that miR-196 may play a role in the malignant progression of gliomas and may be a prognostic predictor in GBMs.
- Received February 9, 2010.
- Revision received June 4, 2010.
- Accepted June 23, 2010.