Isocitrate dehydrogenase 1 (IDH1) mutation-specific microRNA signature predicts favorable prognosis in glioblastoma patients with IDH1 wild type

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Abstract

Background

To date, no prognostic microRNAs (miRNAs) for isocitrate dehydrogenase 1 (IDH1) wild-type glioblastoma multiformes (GBM) have been reported. The aim of the present study was to identify a miRNA signature of prognostic value for IDH1 wild-type GBM patients using miRNA expression dataset from the The Cancer Genome Atlas (TCGA).

Methods

Differential expression profiling analysis of miRNAs was performed on samples from 187 GBM patients, comprising 17 mutant-type IDH1 and 170 wild-type IDH1 samples.

Results

A 23-micoRNA signature which was specific to the IDH1 mutation was revealed. Survival data was available for 140 of the GBM patients with wild-type IDH1. Using these data, the samples were characterized as high-risk or low-risk group according to the ranked protective scores for each of the 23 miRNAs in the 23-miRNA signature. Then, the 23 IDH1 mutation-specific miRNAs were classified as risky group and protective group miRNAs based on the significance analysis of microarrays d-score (SAM d-value) (positive value or negative value). The risky group miRNAs were found to be expressed more in the high-risk samples while the protective group miRNAs were expressed more in the low-risk samples. Patients with high protective scores had longer survival times than those with low protective scores.

Conclusion

These findings show that IDH1 mutation-specific miRNA signature is a marker for favorable prognosis in primary GBM patients with the IDH1 wild type.

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Most cited references 19

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Role of microRNAs in vascular diseases, inflammation, and angiogenesis.

Carmen Urbich, Angelika Kuehbacher, Stefanie Dimmeler (2008)

The integrity of the endothelial monolayer is fundamental for the homoeostasis of the vascular system. Functional endothelial cells are also required for the growth of new blood vessels during neovascularization. Although multiple growth factors have been shown to regulate angiogenesis and vascular development, little is known about the complex upstream regulation of gene expression and translation. MicroRNAs (miRNAs) are an emerging class of highly conserved, non-coding small RNAs that regulate gene expression on the post-transcriptional level by inhibiting the translation of protein from mRNA or by promoting the degradation of mRNA. More than 500 human miRNAs have been identified so far, and increasing evidence indicates that miRNAs have distinct expression profiles and play crucial roles in various physiological and pathological processes such as cardiogenesis, haematopoietic lineage differentiation, and oncogenesis. Meanwhile, a few specific miRNAs that regulate endothelial cell functions and angiogenesis have been described. Let7-f, miR-27b, and mir-130a were identified as pro-angiogenic miRNAs. In contrast, miR-221 and miR-222 inhibit endothelial cell migration, proliferation, and angiogenesis in vitro by targeting the stem cell factor receptor c-kit and indirectly regulating endothelial nitric oxide synthase expression. Moreover, some miRNAs are involved in tumour angiogenesis such as the miR-17-92 cluster and miR-378. Early studies also indicate the contribution of specific miRNAs (e.g. miR-155, miR-21, and miR-126) to vascular inflammation and diseases. Thus, the identification of miRNAs and their respective targets may offer new therapeutic strategies to treat vascular diseases such as atherosclerosis, to improve neovascularization after ischaemia, or to prevent tumour progression.

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High expression of miR-21 and miR-155 predicts recurrence and unfavourable survival in non-small cell lung cancer.

Liguang Wang, Miaomiao Yang, Yang Ni … (2013)

We synthesised the evidence of microRNAs as prognostic biomarkers in lung cancer. Studies were identified by searching PubMed, Embase and Web of Science until March 2012. Descriptive characteristics for studies were described and an additional meta-analysis for two specific microRNAs (miR-21 and miR-155) which were studied extensively was performed. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. The median study size was 88 patients (interquartile range [IQR]=53-193) and the median HR in the studies that reported statistically significant results was 2.855 (IQR=2.01-5.035). For the studies evaluating miR-21's association with clinical outcomes, the pooled HR suggested that high expression of miR-21 has a negative impact on overall survival (OS) in non-small cell lung cancer (NSCLC) (HR=2.32[1.17-4.62], P 0.05) which was not statistically significant, but for RFS/CSS was 1.42 (95% CI: 1.10-1.83, P=0.007). These results indicate that microRNAs show promising associations with prognosis in lung cancer; moreover, specific microRNAs such as miR-21 and miR-155 can predict recurrence and poor survival in NSCLC. Copyright © 2012 Elsevier Ltd. All rights reserved.

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A Ten-microRNA Expression Signature Predicts Survival in Glioblastoma

Sujaya Srinivasan, Irene Rosita Pia Patric, Kumaravel Somasundaram (2011)

Glioblastoma (GBM) is the most common and aggressive primary brain tumor with very poor patient median survival. To identify a microRNA (miRNA) expression signature that can predict GBM patient survival, we analyzed the miRNA expression data of GBM patients (n = 222) derived from The Cancer Genome Atlas (TCGA) dataset. We divided the patients randomly into training and testing sets with equal number in each group. We identified 10 significant miRNAs using Cox regression analysis on the training set and formulated a risk score based on the expression signature of these miRNAs that segregated the patients into high and low risk groups with significantly different survival times (hazard ratio [HR] = 2.4; 95% CI = 1.4–3.8; p<0.0001). Of these 10 miRNAs, 7 were found to be risky miRNAs and 3 were found to be protective. This signature was independently validated in the testing set (HR = 1.7; 95% CI = 1.1–2.8; p = 0.002). GBM patients with high risk scores had overall poor survival compared to the patients with low risk scores. Overall survival among the entire patient set was 35.0% at 2 years, 21.5% at 3 years, 18.5% at 4 years and 11.8% at 5 years in the low risk group, versus 11.0%, 5.5%, 0.0 and 0.0% respectively in the high risk group (HR = 2.0; 95% CI = 1.4–2.8; p<0.0001). Cox multivariate analysis with patient age as a covariate on the entire patient set identified risk score based on the 10 miRNA expression signature to be an independent predictor of patient survival (HR = 1.120; 95% CI = 1.04–1.20; p = 0.003). Thus we have identified a miRNA expression signature that can predict GBM patient survival. These findings may have implications in the understanding of gliomagenesis, development of targeted therapy and selection of high risk cancer patients for adjuvant therapy.

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Author and article information

Contributors

Zheng Wang

Zhaoshi Bao

Wei Yan

Gan You

Yinyan Wang

Xuejun Li

Wei Zhang

Journal

Journal ID (nlm-ta): J Exp Clin Cancer Res

Journal ID (iso-abbrev): J. Exp. Clin. Cancer Res

Title: Journal of Experimental & Clinical Cancer Research : CR

Publisher: BioMed Central

ISSN (Print): 0392-9078

ISSN (Electronic): 1756-9966

Publication date Collection: 2013

Publication date (Electronic): 29 August 2013

Volume: 32

Issue: 1

Page: 59

Affiliations

[1 ]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, Beijing 100050, China

[2 ]Beijing Neurosurgical Institute, No. 6 Tiantan Xili, Dongcheng District, Beijing 100050, China

[3 ]Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China

Article

Publisher ID: 1756-9966-32-59

DOI: 10.1186/1756-9966-32-59

PMC ID: 3847806

PubMed ID: 23988086

SO-VID: dd7b6175-a87a-4437-b475-8cd3c9649ecc

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Isocitrate dehydrogenase 1 (IDH1) mutation-specific microRNA signature predicts favorable prognosis in glioblastoma patients with IDH1 wild type

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Abstract

Background

Methods

Results

Conclusion

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Karger: Oncology

Most cited references 19

Role of microRNAs in vascular diseases, inflammation, and angiogenesis.

High expression of miR-21 and miR-155 predicts recurrence and unfavourable survival in non-small cell lung cancer.

A Ten-microRNA Expression Signature Predicts Survival in Glioblastoma

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