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.
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.
['Maimaiti|Aierpati|A|', 'Wang|Xixian|X|', 'Pei|Yinan|Y|', 'Nuermaimaiti|Nuerbiye|N|', 'Tuersunniyazi|Abudireheman|A|', 'Abula|Yaeraili|Y|', 'Feng|Zhaohai|Z|', 'Jiang|Lei|L|', 'Shi|Xin|X|', 'Kasimu|Maimaitijiang|M|']
D000328:Adult D019540:Area Under Curve D014408:Biomarkers, Tumor D001932:Brain Neoplasms D005260:Female D000091344:Filaggrin Proteins D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D042822:Genomic Instability D005910:Glioma D006801:Humans D007521:Isocitrate Dehydrogenase D053208:Kaplan-Meier Estimate D008297:Male D015999:Multivariate Analysis D009154:Mutation D060787:Neoplasm Grading D011379:Prognosis D016016:Proportional Hazards Models D062085:RNA, Long Noncoding D012333:RNA, Messenger D012372:ROC Curve D015203:Reproducibility of Results
long non-coding RNA (lncRNA) low-grade glioma (LGG) genomic instability-associated lncRNAs signature (GILncSig) prognosis risk score