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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Risk Score based on microRNA expression signature is independent prognostic classifier of glioblastoma patients
Jiri Sana1, Lenka Radova2, Radek Lakomy3
1Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno 65653, Czech Republic, Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic, Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic.
Abstract:
Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. The prognosis of GBM patients varies considerably and the histopathological examination is not sufficient for individual risk estimation. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and were repeatedly proved to play important roles in pathogenesis of GBM. In our study, we performed global miRNA expression profiling of 58 glioblastoma tissue samples obtained during surgical resections and 10 non-tumor brain tissues. The subsequent analysis revealed 28 significantly deregulated miRNAs in GBM tissue, which were able to precisely classify all examined samples. Correlation with clinical data led to identification of six-miRNA signature significantly associated with progression free survival [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.33-2.94, P < 0.001] and overa+ll survival (HR 2.86, 95% CI 1.91-4.29, P < 0.001). O(6)-methylguanine-DNA methyltransferase methylation status was evaluated as reference method and Risk Score based on six-miRNA signature indicated significant superiority in prediction of clinical outcome in GBM patients. Multivariate Cox analysis indicated that the Risk Score based on six-miRNA signature is an independent prognostic classifier of GBM patients. We suggest that the Risk Score presents promising prognostic algorithm with potential for individualized treatment decisions in clinical management of GBM patients.
Insights
A novel six-microRNA (miRNA) signature accurately predicts glioblastoma multiforme (GBM) patient survival. This miRNA-based risk score outperforms standard methods, offering a promising tool for personalized GBM treatment decisions.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with variable patient prognosis.
- Histopathology alone is insufficient for accurate individual risk stratification in GBM.
- MicroRNAs (miRNAs) are key regulators implicated in GBM pathogenesis.
Purpose of the Study:
- To identify novel biomarkers for predicting GBM patient outcomes.
- To develop a miRNA-based prognostic model for clinical application.
- To compare the predictive power of a miRNA signature against established methods.
Main Methods:
- Global miRNA expression profiling of 58 GBM tissues and 10 non-tumor brain tissues.
- Identification of significantly deregulated miRNAs and correlation with clinical data.
- Development and validation of a six-miRNA signature-based Risk Score.
Main Results:
- 28 miRNAs were significantly deregulated in GBM tissues.
- A six-miRNA signature accurately classified all samples and was strongly associated with progression-free and overall survival.
- The miRNA-based Risk Score demonstrated superior predictive accuracy compared to O(6)-methylguanine-DNA methyltransferase methylation status.
Conclusions:
- The developed six-miRNA signature serves as an independent prognostic classifier for GBM patients.
- The miRNA-based Risk Score shows potential as a prognostic algorithm for guiding individualized treatment strategies.
- This approach may enhance clinical management and decision-making for GBM patients.
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