Abstract
MicroRNAs (miRNAs) may act as prognostic biomarkers in a variety of cancers. The aim of this study was to identify and evaluate a prognostic miRNA signature in patients with lower-grade gliomas (LGGs). miRNA expression profiles and clinical data of patients with LGGs from the Chinese Glioma Genome Atlas (CGGA; the training cohort) and The Cancer Genome Atlas (TCGA; the validation cohort) were analyzed, and the least absolute shrinkage and selection operator Cox regression model was used to identify the miRNA signature, which was combined with clinical prognostic factors to develop an individualized survival prediction model. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to reveal the biological implications of the signature. We identified a four-miRNA signature that stratified patients in the training cohort into low- or high-risk groups according to overall survival time, a finding that was verified in the validation cohort. Multivariate Cox regression analysis indicated that the four-miRNA signature was an independent prognostic biomarker, and a nomogram combining this miRNA signature with clinicopathological and molecular factors showed high prognostic accuracy for individualized survival prediction in both TCGA (C-index = 0.83) and CGGA (C-index = 0.68) cohorts. Functional annotation indicated that the major biological processes of this prognostic miRNA signature were enriched in cell cycle and DNA repair-associated biological processes. Our findings indicated that our newly discovered four-miRNA signature may be an effective independent prognostic factor for the prediction of patients with LGGs.
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The authors conducting this work represent the Chinese Glioma Cooperative Group (CGCG).
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This work was supported by Beijing Postdoctoral Research Foundation (2016ZZ-37).
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The glioma tissue collection was approved by the Institutional Review Board of Beijing Tiantan Hospital affiliated to Capital Medical University.
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11060_2017_2704_MOESM1_ESM.tif
Fig S1. The prognostic value of the four-miRNA signature in the three molecular subgroups of LGGs. (A) Scatter plot demonstrating that the risk score was distributed differently in the three molecular subgroups. The signature enabled the segmentation of patients into high- and low-risk groups in the (B) IDHMUT +1p/19q codel, (C) IDHMUT +1p/19q non-codel, and (D) IDHWT subgroups (TIF 1460 KB)
11060_2017_2704_MOESM2_ESM.tif
Fig S2. Figure showing significant functions and pathway enrichment analysis of the four-miRNA signature in the validation dataset. (A) Heat map of differentially expressed genes between high- and low-risk four-miRNA signature groups from 420 LGG samples. (B) Network analysis and (C) gene ontology analysis showing that high-risk was associated with specific biological processes. (D) Pathway enrichment analysis showing that the high-risk group was associated with several KEGG pathways, including cell cycle and DNA replication (TIF 57539 KB)
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Qian, Z., Li, Y., Fan, X. et al. Prognostic value of a microRNA signature as a novel biomarker in patients with lower-grade gliomas. J Neurooncol 137, 127–137 (2018). https://doi.org/10.1007/s11060-017-2704-5
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DOI: https://doi.org/10.1007/s11060-017-2704-5