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Expression and prognostic value of microRNAs in lower-grade glioma depends on IDH1/2 status

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Abstract

Histological and genomic characteristics are widely used in glioma management and research. This study investigated their relationship to the expression and prognostic value of microRNAs (miRNAs) in lower-grade glioma (LGG). A total of 447 LGG samples with available clinical and genomic information from The Cancer Genome Atlas database were reviewed. Samples with isocitrate dehydrogenase (IDH) 1/2 mutations (n = 366) were randomly divided into training and validation sets to establish and confirm a four-miRNA-based risk classifier. We found that IDH1/2 mutation status had greater impact than histological and other genomic features on miRNA expression patterns; 361/487 (74%) of miRNAs were differentially expressed according to IDH1/2 mutation status. Importantly, there were no miRNAs with the same prognostic significance among groups with different IDH1/2 mutation status. For IDH1/2-mut LGG, a four-miRNA risk classifier (miR-10b, miR-130b, miR-1304, and miR-302b) was established that could independently distinguish cases as high or low risk of poor prognosis in both training and validation sets. The risk classifier outperformed individual miRNAs and traditional prognostic factors in terms of sensitivity and specificity. Bioinformatic analyses indicated that high-risk samples were more mitotically active than low-risk samples. Taken together, IDH1/2 mutation status had a significant influence on miRNA expression and prognostication in LGG. The four-miRNA-based risk classifier can be used for risk stratification of IDH1/2-mut LGG.

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Acknowledgements

The authors conducting this work represent the Chinese Glioma Cooperative Group (CGCG).

Funding

This work was funded by grants from the National Natural Science Foundation of China (Grant Numbers: 81172409, 81472360, and 81402045) and the Science and Technology Department of Liaoning Province (Grant No. 2011225034).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang, 110001, China

    Wen Cheng, Sheng Han & Anhua Wu

  2. Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China

    Xiufang Ren

  3. Beijing Neurosurgical Institute, Capital Medical University, Beijing, China

    Chuanbao Zhang

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  1. Wen Cheng
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Correspondence to Anhua Wu.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards

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Cheng, W., Ren, X., Zhang, C. et al. Expression and prognostic value of microRNAs in lower-grade glioma depends on IDH1/2 status. J Neurooncol 132, 207–218 (2017). https://doi.org/10.1007/s11060-016-2368-6

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