A ten-microRNA expression signature predicts survival in glioblastoma - PubMed (original) (raw)

A ten-microRNA expression signature predicts survival in glioblastoma

Sujaya Srinivasan et al. PLoS One. 2011.

Abstract

Glioblastoma (GBM) is the most common and aggressive primary brain tumor with very poor patient median survival. To identify a microRNA (miRNA) expression signature that can predict GBM patient survival, we analyzed the miRNA expression data of GBM patients (n=222) derived from The Cancer Genome Atlas (TCGA) dataset. We divided the patients randomly into training and testing sets with equal number in each group. We identified 10 significant miRNAs using Cox regression analysis on the training set and formulated a risk score based on the expression signature of these miRNAs that segregated the patients into high and low risk groups with significantly different survival times (hazard ratio [HR]=2.4; 95% CI=1.4-3.8; p<0.0001). Of these 10 miRNAs, 7 were found to be risky miRNAs and 3 were found to be protective. This signature was independently validated in the testing set (HR=1.7; 95% CI=1.1-2.8; p=0.002). GBM patients with high risk scores had overall poor survival compared to the patients with low risk scores. Overall survival among the entire patient set was 35.0% at 2 years, 21.5% at 3 years, 18.5% at 4 years and 11.8% at 5 years in the low risk group, versus 11.0%, 5.5%, 0.0 and 0.0% respectively in the high risk group (HR=2.0; 95% CI=1.4-2.8; p<0.0001). Cox multivariate analysis with patient age as a covariate on the entire patient set identified risk score based on the 10 miRNA expression signature to be an independent predictor of patient survival (HR=1.120; 95% CI=1.04-1.20; p=0.003). Thus we have identified a miRNA expression signature that can predict GBM patient survival. These findings may have implications in the understanding of gliomagenesis, development of targeted therapy and selection of high risk cancer patients for adjuvant therapy.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Kaplan-Meier survival estimates overall survival of glioblastoma patients according to the 10 miRNA expression signature.

A) 111 GBM patients in the training data set. B) 111 GBM patients in the testing data set.

Figure 2. Ten miRNA Risk-Score Analysis of 111 GBM patients (training set).

A) Heat map of ten miRNA expression profiles of GBM patients; rows represent risky and protective miRNAs, and columns represent patients. The blue line represents the miRNA signature cutoff dividing patients into low-risk and high-risk groups. B) Patient survival status along with risk score. C) miRNA risk-score distribution of the GBM patients.

Figure 3. Ten miRNA Risk-Score Analysis of 111 GBM patients (test set).

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A ten-microRNA expression signature predicts survival in glioblastoma - PubMed (original) (raw)