Correlation of MicroRNA 132 Up-regulation with an Unfavorable Clinical Outcome in Patients with Primary Glioblastoma Multiforme Treated with Radiotherapy Plus Concomitant and Adjuvant Temozolomide Chemotherapy

Parker, Nicole; Correia, Nelson; Crossley, Brendan; Buckland, Michael E.; Howell, Viive M.; Wheeler, Helen

doi:10.1593/tlo.13553

Cited by 31 publications

(20 citation statements)

References 47 publications

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“…More than 1500 human miRNAs have been identified and many are now known to be up-or down-regulated in various cancers. Indeed, several miRNA have been implicated in glioblastoma development, progression and as a potential prognostic biomarker (28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA as potential biomarkers in Glioblastoma

et al. 2015

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Glioblastoma is the most aggressive and lethal tumour of the central nervous system and as such the identification of reliable prognostic and predictive biomarkers for patient survival and tumour recurrence is paramount. MicroRNA detection has rapidly emerged as potential biomarkers, in patients with glioblastoma. Over the last decade, analysis of miRNA in laboratory based studies have yielded several candidates as potential biomarkers however, the accepted use of these candidates in the clinic is yet to be validated. Here we will examine the use of miRNA signatures to improve glioblastoma stratification into subgroups and summarise recent advances made in miRNA examination as potential biomarkers for glioblastoma progression and recurrence.

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Section: Introductionmentioning

confidence: 99%

MicroRNA as potential biomarkers in Glioblastoma

et al. 2015

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“…Among the other panel‐associated miRNAs, some have been reported to be implicated in glioma biology. MiR‐132 was upregulated in GBMs and was a potential indicator of poor prognosis . MiR‐127 and miR‐433 are both derived from an overlapping gene locus and colocalized within a cancer‐associated genomic region .…”

Section: Discussionmentioning

confidence: 99%

A five‐CpG signature of microRNA methylation in non‐G‐CIMP glioblastoma

Kang

Yin

et al. 2019

CNS Neurosci Ther

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Summary Aims DNA methylation has been found to regulate microRNAs (miRNAs) expression, but the prognostic value of miRNA‐related DNA methylation aberration remained largely elusive in cancers including glioblastomas (GBMs). This study aimed to investigate the clinical and biological feature of miRNA methylation in GBMs of non‐glioma‐CpG island methylator phenotype (non‐G‐CIMP). Methods Prognostic miRNA methylation loci were analyzed, with TCGA and Rennes cohort as training sets, and independent datasets of GBMs and low‐grade gliomas (LGGs) were obtained as validation sets. Different statistical and bioinformatic analysis and experimental validations were performed to clinically and biologically characterize the signature. Results We identified and validated a risk score based on methylation status of five miRNA‐associated CpGs which could predict survival of GBM patients in a series of training and validation sets. This signature was independent of age and O‐6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation status. The risk subgroup was associated with angiogenesis and accordingly differential responses to bevacizumab‐contained therapy. MiRNA target analysis and in vitro experiments further confirmed the accuracy of this signature. Conclusion The five‐CpG signature of miRNA methylation was biologically relevant and was of potential prognostic and predictive value for GBMs. It might be of help for improving individualized treatment.

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“…Previous studies have investigated the prognostic roles of the five miRNAs constituting our classifier. In particular, miR-222, -145, and -132 have prognostic significance for GBM patients [ 23 - 25 ]. MiR-222, always along with miR-221, confers a malignant phenotype in GBM [ 26 - 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…MiR-20a has been reported to be expressed at high level in glioma stem cell and enhances the self-renewal of human glioma cells [ 7 , 33 ]. MiR-132 confers unfavorable prognosis in GBM and is involved in several important functions in other types of cancer, such as angiogenesis, inflammation, and tumorigenesis [ 25 ]. MiR-129 has low expression in glioma cells and serves as a tumor suppressor by inhibiting cell growth and invasion [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

A five-miRNA signature with prognostic and predictive value for MGMT promoter-methylated glioblastoma patients

et al. 2015

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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 profiles. The present study aimed to refine the prognostic and predictive value of MGMT promoter status in GBM by identifying a micro (mi)RNA risk signature. Data from The Cancer Genome Atlas was used for this study, with MGMT promoter-methylated samples randomly divided into training and internal validation sets. Data from The Chinese Glioma Genome Atlas was used for independent validation. A five miRNA-based risk signature was established for MGMT promoter-methylated GBM to distinguish cases as high- or low-risk with distinct prognoses, which was confirmed using internal and external validation sets. Importantly, the prognostic value of the signature was significant in different cohorts stratified by clinicopathologic factors and alkylating chemotherapy, and a multivariate Cox analysis found it to be an independent prognostic marker along with age and chemotherapy. Based on these three factors, we developed a quantitative model with greater accuracy for predicting the 1-year survival of patients with MGMT promoter-methylated GBM. These results indicate that the five-miRNA signature is an independent risk predictor for GBM with MGMT promoter methylation and can be used to identify patients at high risk of unfavorable outcome and resistant to alkylating chemotherapy, underscoring its potential for personalized GBM management.

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Correlation of MicroRNA 132 Up-regulation with an Unfavorable Clinical Outcome in Patients with Primary Glioblastoma Multiforme Treated with Radiotherapy Plus Concomitant and Adjuvant Temozolomide Chemotherapy

Abstract: This study identified high miR-132 expression as a biomarker of poor prognosis in patients with primary GBM treated with the Stupp regimen.

Cited by 31 publications

References 47 publications

MicroRNA as potential biomarkers in Glioblastoma

MicroRNA as potential biomarkers in Glioblastoma

A five‐CpG signature of microRNA methylation in non‐G‐CIMP glioblastoma

A five-miRNA signature with prognostic and predictive value for MGMT promoter-methylated glioblastoma patients

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