A 4-miRNAs signature predicts survival in glioblastoma multiforme patients

Yuan, Guoqiang; Wei, Ning; Mu, Linsen; Wang, X.Q.; Zhang, Y.N.; Zhou, Wangning; Pan, Yunyan

doi:10.3233/cbm-170205

Cited by 26 publications

(23 citation statements)

References 42 publications

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“…In that regard, previous studies detected GBM-associated EVs in patient plasma (Jones et al, 2019), elevated levels of miR-9 in GBM tissues (Wu et al, 2013) and in the serum-derived EVs (Ji et al 2016) and cerebrospinal fluid (CSF) (Sørensen et al 2017) of acute ischemic stroke patients, suggesting miR-9 as a potential liquid biopsy marker for GBM progression and brain damage. The prognostic value of miR-9 levels has already been endorsed with its inclusion in multi-marker prognostic panels for GBM (Yuan et al, 2017). Our study supports these results by providing a mechanistic role of miR-9 in GBM progression.…”

Section: Discussionsupporting

confidence: 86%

Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells

et al. 2020

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Graphical AbstractHighlights d GBM EVs and growth factors promote angiogenesis by distinct pathways d EV-exposed endothelial cells show a footprint of gene regulation by EV miRNAs d The EV miRNA pathway explains failure of anti-angiogenic therapy for GBM d The results suggest an angiogenic pathway and liquid biopsy biomarkers for GBM SUMMARY Glioblastoma (GBM) is characterized by aberrant vascularization and a complex tumor microenvironment. The failure of anti-angiogenic therapies suggests pathways of GBM neovascularization, possibly attributable to glioblastoma stem cells (GSCs) and their interplay with the tumor microenvironment. It has been established that GSC-derived extracellular vesicles (GSC-EVs) and their cargoes are proangiogenic in vitro. To further elucidate EV-mediated mechanisms of neovascularization in vitro, we perform RNA-seq and DNA methylation profiling of human brain endothelial cells exposed to GSC-EVs. To correlate these results to tumors in vivo, we perform histoepigenetic analysis of GBM molecular profiles in the TCGA collection. Remarkably, GSC-EVs and normal vascular growth factors stimulate highly distinct gene regulatory responses that converge on angiogenesis. The response to GSC-EVs shows a footprint of post-transcriptional gene silencing by EV-derived miRNAs. Our results provide insights into targetable angiogenesis pathways in GBM and miRNA candidates for liquid biopsy biomarkers.

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Section: Discussionsupporting

confidence: 86%

Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells

et al. 2020

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“…On the other hand, Yuan et al [57] found increased levels of let-7g-5p, miR-139-5p, miR-17-5p, and miR-9-3p in tumor tissue samples from long-term glioblastoma survivors independent of their MGMT methylation status. Patients with high expression levels of these miRNAs lived 88 days longer than patients with low expression levels (439 vs. 351 days, respectively) [57].…”

Section: Long-term Glioblastoma Survivorsmentioning

confidence: 97%

“…This can be partially explained with better overall health, but it can also be a result of different molecular and genetic alterations in younger compared to older patients [5]. Although glioblastomas from short-and long-term survivors are histologically the same, their biological and molecular characteristics are remarkably different [57].…”

Section: Long-term Glioblastoma Survivorsmentioning

confidence: 99%

“…Regarding the association between genetic mutations and survival, reports show that glioblastomas with IDH1/2 mutations and MGMT promoter methylation are more responsive to surgical resection and temozolomide chemotherapy, and have better prognosis [57,[64][65][66]. Hartmann et al compared tumor samples from 33 patients with primary glioblastoma who lived longer than 60 months to patients whose OS was not longer than 36 months [67].…”

Section: Long-term Glioblastoma Survivorsmentioning

confidence: 99%

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Genetic secrets of long-term glioblastoma survivors

Jovčevska

2018

Bosn J of Basic Med Sci

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Glioblastomas account for the majority of primary brain tumors. Although glioblastomas are considered as rare diseases, they represent 60%-70% of all gliomas and in most cases have fatal consequences. Genetic analyses show great heterogeneity both intratumor and intertumor. This notion opens up debates about glioblastoma origin. Different brain cells including astrocytes, neural stem cells, oligodendrocyte precursor cells and glioblastoma stem cells are proposed as capable of initiation and reseeding a tumor; however data is still inconclusive. Due to high mortality rate, long term glioblastoma survivors are defined as patients who live longer than 2 years post diagnosis. Extreme survivors, living 10 years or more after diagnosis, comprise less than 1% of all patients. Molecular testing suggests differences in the genetic profiles of glioblastoma between short and long term survivors. The most informative indicators are IDH mutations and MGMT promotor methylation. Other genes like FBLN4, EMP3, IGFBP-2, IGFBP-3, LGALS3, MAOB, PDPN, SERPING1 and TIMP1 have also been associated with glioblastoma prolonged survival. Emerging evidence proposes roles of different microRNAs in predicting patient survival. Moreover, clinical features like seizures as a symptom at presentation, age at diagnosis, and the extent of the surgical resection are also factors that influence the length of survival. Because of the small number of long term survivors, it is difficult to examine these samples and draw conclusions about the genetics of glioblastoma longevity. To aid in the clinical care, a thorough "omics" approach is necessary for identifying differences between short and long term glioblastoma survivors.

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“…Accumulating studies have identified multiple dysregulated miRNAs, which may serve as key molecules in cancer progression, and regulate various biological processes, including proliferation, differentiation, apoptosis and survival (8)(9)(10). Previous studies have demonstrated a significant difference in the expression profile of miRNAs between healthy subjects and patients with glioma, suggesting that the expression levels of certain miRNAs are associated with the overall survival (OS) of glioma patients (11)(12)(13)(14). Therefore, the identification of differentially expressed miRNAs is of great importance in order to evaluate the early prognosis of glioma patients.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of microRNA‑374a predicts poor prognosis in human glioma

et al. 2019

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Certain microRNAs (miRNAs/miRs) may be used as prognostic biomarkers in various types of cancer. The purpose of the present study was to identify miRNAs that were abnormally expressed in glioma of different grades, and to evaluate their clinical implications in patients with glioma. The differentially expressed miRNAs were evaluated from the expression profiles of six glioma tissues (three low-grade and three high-grade gliomas) determined using a microarray platform. Reverse transcription-quantitative polymerase chain reaction analysis was used to further verify the aberrant expression of the candidate miRNA in a set of 42 patients and 5 healthy controls. The miRNA target genes were predicted and the protein-protein interaction network was generated; furthermore, functional enrichment analysis of the target genes in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed. Kaplan-Meier curves and Log-rank analysis, as well as multivariate Cox regression analysis were performed to assess the association of the candidate miRNA with patient survival. A total of 15 differentially expressed miRNAs, including 13 downregulated and 2 upregulated miRNAs, were identified by comparison of low-grade and high-grade glioma tissues. The miR-374a expression of high-grade gliomas was significantly lower than that of low-grade gliomas (fold change, -4.43; P=0.027). The expression levels of miR-374a gradually decreased with the increase of the pathological grade of glioma. Pearson's Chi-square test was used to determine the association of miR-374a expression with several clinicopathological factors. Furthermore, low expression of miR-374a was determined to be an independent prognostic marker and that it was significantly associated with overall survival (P=0.0213). GO and KEGG pathway analysis revealed that the target genes of miR-374a may be involved in the regulation of the RNA polymerase II promoter and mTOR signaling pathway. The four hub genes (CCND1, SP1, CDK4, CDK6) were also identified by PPI network analysis. In conclusion, the present study indicated that miR-374a may be used as a promising prognostic biomarker for the screening of high-risk populations and for the assessment of the prognosis of patients with glioma.

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A 4-miRNAs signature predicts survival in glioblastoma multiforme patients

Abstract: The 4-miRNA signature was identified as an independent prognostic biomarker that identified patients who have a favorable outcome.

Cited by 26 publications

References 42 publications

Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells

Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells

Genetic secrets of long-term glioblastoma survivors

Downregulation of microRNA‑374a predicts poor prognosis in human glioma

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