G Q Yuan1, N L Wei2, L Y Mu3, X Q Wang1, Y N Zhang4, W N Zhou4, Y W Pan1,4. 1. Institute of Neurology, The Second Hospital, Lanzhou University, Lanzhou, Gansu 730030, China. 2. Department of Neurosurgery, Fudan University Huashan Hospital, Fudan University, Shanghai 20040, China. 3. 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. 4. Department of Neurosurgery, The Second Hospital, Lanzhou University, Lanzhou, Gansu 730030, China.
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.
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.
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