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Updated: Feb 23, 2026
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
A 4-miRNAs signature predicts survival in glioblastoma multiforme patients
1Institute of Neurology, The Second Hospital, Lanzhou University, Lanzhou, Gansu 730030, China.
Background:
Although O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation status is an important marker for glioblastoma multiforme (GBM), there is considerable variability in the clinical outcome of patients with similar methylation profles.
Objective:
We examined whether a MicroRNA (miRNA) signature can be identified for predicting clinical outcomes and helping in treatment decisions.
Methods:
The differentially expressed miRNAs were evaluated in 6 pairs of short- (⩽ 450 days) and long-term survivors (> 450 days) by using microarray. Real time quantitative PCR (qRT-PCR) was applied to further verify screened miRNAs with a greater number of samples (n= 48). Meanwhile, functional interpretation of miRNA profile was carried out based on miRNA-target databases. In addition, MGMT promoter methylation status was tested by means of pyrosequencing (PSQ) testing.
Results:
Six miRNAs were upregulated in the long-term survival group (fold change ⩾ 2.0, P< 0.05). The further verification by qRT-PCR indicated that the increase in let-7g-5p, miR-139-5p, miR-17-5p and miR-9-3p level in long-term survivors was statistically significant. Kaplan-Meier survival analysis showed that high expression of a prognostic 4-miRNA signature was significantly associated with good patient survival (p= 0.0012). The signature regulated signaling pathways including Calcium, MAPK, ErbB, mTOR and cell cycle involved in carcinogenesis from glial progenitor cell to primary GBM.
Conclusions:
The 4-miRNA signature was identified as an independent prognostic biomarker that identified patients who have a favorable outcome.
