Research Paper Volume 13, Issue 11 pp 15164—15192
Identification and validation of a novel eight mutant-derived long non-coding RNAs signature as a prognostic biomarker for genome instability in low-grade glioma
- 1 Department of Functional Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China
- 2 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Disease in Central Asia, Department of Biochemistry and Molecular Biology, Basic Medicine College, Xinjiang Medical University, Urumqi, Xinjiang 830054, China
Received: February 18, 2021 Accepted: May 11, 2021 Published: June 3, 2021
https://doi.org/10.18632/aging.203079How to Cite
Copyright: © 2021 Maimaiti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Long non-coding RNAs (lncRNAs) comprise an integral part of the eukaryotic transcriptome. Alongside proteins, lncRNAs modulate lncRNA-based gene signatures of unstable transcripts, play a crucial role as antisense lncRNAs to control intracellular homeostasis and are implicated in tumorigenesis. However, the role of genomic instability-associated lncRNAs in low-grade gliomas (LGG) has not been fully explored. In this study, lncRNAs expression and somatic mutation profiles in low-grade glioma genome were used to identify eight novel mutant-derived genomic instability-associated lncRNAs including H19, FLG-AS1, AC091932.1, AC064875.1, AL138767.3, AC010273.2, AC131097.4 and ISX-AS1. Patients from the LGG gene mutagenome atlas were grouped into training and validation sets to test the performance of the signature. The genomic instability-associated lncRNAs signature (GILncSig) was then validated using multiple external cohorts. A total of 59 novel genomic instability-associated lncRNAs in LGG were used for least absolute shrinkage and selection operator (Lasso), single and multifactor Cox regression analysis using the training set. Furthermore, the independent predictive role of risk features in the training and validation sets were evaluated through survival analysis, receiver operating feature analysis and construction of a nomogram. Patients with IDH1 mutation status were grouped into two different risk groups based on the GILncSig score. The low-risk group showed a relatively higher rate of IDH1 mutations compared with patients in the high-risk group. Furthermore, patients in the low-risk group had better prognosis compared with patients in the high-risk group. In summary, this study reports a reliable prognostic prediction signature and provides a basis for further investigation of the role of lncRNAs on genomic instability. In addition, lncRNAs in the signature can be used as new targets for treatment of LGG.
Abbreviations
LGG: low-grade glioma; lncRNA: long non-coding RNA; GILncSig: Genomic instability-associated lncRNA signature; Lasso: least absolute shrinkage and selection operator; ROC: receiver operating characteristic; AUC: area under the curve; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; OS: overall survival; TCGA: The Cancer Genome Atlas; CGGA: Chinese Glioma Genome Atlas; GEO: Gene Expression Omnibus; GU: genomic unstable; GS: genomic stable.