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.
Highlights
The grade IV astrocytoma, GBM, is the most common and malignant primary adult brain cancer [1]
Further analysis revealed that methylation of MGMT promoter to be the strongest predictor for outcome and benefit from temozolomide chemotherapy [2]
We have identified a ten miRNA signature that is associated with survival of GBM patients. We confirmed these findings in a testing set
Summary
The grade IV astrocytoma, GBM, is the most common and malignant primary adult brain cancer [1]. Despite advances in treatment modalities, the median survival is very poor. Since postoperative radiotherapy alone did not provide great benefit to GBM patients, several attempts have been made to find suitable adjuvant chemotherapy. The present standard treatment appears to be maximal safe resection of the tumor followed by irradiation and temozolomide adjuvant chemotherapy [2]. It was found that not all patients were benefited from the addition of temozolomide. Further analysis revealed that methylation of MGMT promoter to be the strongest predictor for outcome and benefit from temozolomide chemotherapy [2]. Recent molecular and genetic profiling studies have identified several markers and unique signatures as prognostic and predictive factors of GBM [3,4]
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