Abstract

MicroRNAs (miRNAs) are directly involved in the progression in various cancers. To date, no systematic researches have been performed on the expression pattern of miRNA during progression from low grade gliomas to anaplastic gliomas or secondary glioblastomas and those prognostic miRNAs in anaplastic gliomas and secondary glioblastomas. In the present study, high-throughput microarrays were used to measure miRNA expression levels in 116 samples in the different progression stages of glioma. We found that miRNA expression pattern totally altered when low grade gliomas progressed to anaplastic gliomas or secondary glioblastomas. However, anaplastic gliomas and secondary glioblastomas have similar expression pattern in miRNA level. Furthermore, we developed a five-miRNA signature (two protective miRNAs-miR-767-5p, miR-105; three risky miRNAs: miR-584, miR-296-5p and miR-196a) that could identify patients with a high risk of unfavorable outcome in anaplastic gliomas regardless of histology type. It should be highlighted that the five-miRNA signature can also identify patients who had a high risk of unfavorable outcome in secondary and TCGA Proneural glioblastomas, but not Neural, Classical and Mesenchymal glioblastomas. Taken together, our results demonstrate that miRNA expression patterns in the malignant progression of gliomas and a novel prognostic classifier, the five-miRNA signature, serve as a prognostic marker for patient risk stratification in anaplastic gliomas, Secondary and Proneural glioblastomas.

Highlights

  • We found that miRNA expression pattern totally altered when low grade gliomas progressed to anaplastic gliomas or secondary glioblastomas

  • Samples were ordered from low grade glioma to secondary glioblastomas, and significant genes were clustered (Figure 1)

  • We analyzed the whole-genome miRNA profiles 116 samples in the different progression stages of glioma and found that miRNA expression pattern totally altered when low grade gliomas progressed to anaplastic gliomas or secondary glioblastomas

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Summary

Introduction

MicroRNAs (miRNAs) belong to a recently discovered class of small, non-coding RNA molecules that regulate the expression of multiple target genes and multiple cellular processes including cell differentiation, stem cell maintenance, and epithelial–mesenchymal transition.[1, 2] The abnormal expression of miRNAs is a common feature of cancers and can be caused by different mechanisms such as amplification/deletion, chromosomal rearrangements, and epigenetic regulation.[3, 4] Depending on the genes targeted, miRNAs can act as either oncogenes or tumor suppressors.[5,6,7,8] MiRNAs show characteristic expression signatures in various cancers and can profoundly affect cancer cell behavior[9, 10]. We found that miRNA expression pattern totally altered when low grade gliomas progressed to anaplastic gliomas or secondary glioblastomas.

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