Mutation-derived, genomic instability-associated lncRNAs are prognostic markers in gliomas.

Abstract

Gliomas are the most commonly-detected malignant tumors of the brain. They contain abundant long non-coding RNAs (lncRNAs), which are valuable cancer biomarkers. LncRNAs may be involved in genomic instability; however, their specific role and mechanism in gliomas remains unclear. LncRNAs that are related to genomic instability have not been reported in gliomas. The transcriptome data from The Cancer Genome Atlas (TCGA) database were analyzed. The co-expression network of genomic instability-related lncRNAs and mRNA was established, and the model of genomic instability-related lncRNA was identified by univariate Cox regression and LASSO analyses. Based on the median risk score obtained in the training set, we divided the samples into high-risk and low-risk groups and proved the survival prediction ability of genomic instability-related lncRNA signatures. The results were verified in the external data set. Finally, a real-time quantitative polymerase chain reaction assay was performed to validate the signature. The signatures of 17 lncRNAs (LINC01579, AL022344.1, AC025171.5, LINC01116, MIR155HG, AC131097.3, LINC00906, CYTOR, AC015540.1, SLC25A21.AS1, H19, AL133415.1, SNHG18, FOXD3.AS1, LINC02593, AL354919.2 and CRNDE) related to genomic instability were identified. In the internal data set and Gene Expression Omnibus (GEO) external data set, the low-risk group showed better survival than the high-risk group (P < 0.001). In addition, this feature was identified as an independent risk factor, showing its independent prognostic value with different clinical stratifications. The majority of patients in the low-risk group had isocitrate dehydrogenase 1 (IDH1) mutations. The expression levels of these lncRNAs were significantly higher in glioblastoma cell lines than in normal cells. Our study shows that the signature of 17 lncRNAs related to genomic instability has prognostic value for gliomas and could provide a potential therapeutic method for glioblastoma.