Affiliations: [a] Institute of Neurology, The Second Hospital, Lanzhou University, Lanzhou, Gansu 730030, China | [b] Department of Neurosurgery, Fudan University Huashan Hospital, Fudan University, Shanghai 20040, China | [c] Institute of Biochemistry and Molecular Biology, School of Life Sciences, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou, Gansu 730000, China | [d] Department of Neurosurgery, The Second Hospital, Lanzhou University, Lanzhou, Gansu 730030, China
Correspondence:
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Corresponding author: Y.W. Pan, Institute of Neurology, The Second Hospital, Lanzhou University, Lanzhou, Gansu 730030, China. E-mail: [email protected].
Abstract: 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.
