Long Non-coding RNA Expression Profiling Identifies a Four-Long Non-coding RNA Prognostic Signature for Isocitrate Dehydrogenase Mutant Glioma

长链非编码RNA表达谱分析鉴定出异柠檬酸脱氢酶突变型胶质瘤的四种长链非编码RNA预后特征

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Abstract

Background: Isocitrate dehydrogenase (IDH) mutant is one of the most robust and important genetic aberrations in glioma. However, the underlying regulation mechanism of long non-coding RNA (lncRNA) in IDH mutant glioma has not been systematically portrayed. Methods:In this work, 775 IDH mutant glioma samples with transcriptome data, including 167 samples from the Chinese Glioma Genome Atlas (CGGA) RNAseq dataset, 390 samples from The Cancer Genome Atlas (TCGA) dataset, 79 samples from GSE16011 dataset, and 139 samples from CGGA microarray dataset, were enrolled. R language and GraphPad Prism software were applied for the statistical analysis and graphical work. Results: By comparing the differentially lncRNA genes between IDH mutant and IDH wild-type glioma samples, a four-lncRNA (JAG1, PVT1, H19, and HAR1A) signature was identified in IDH mutant glioma patients. The signature model was established based on the expression level and the regression coefficient of the four lncRNA genes. IDH mutant glioma samples could be successfully stratified into low-risk and high-risk groups in CGGA RNAseq, TCGA, GSE16011, and CGGA microarray databases. Meanwhile, multivariate Cox analysis showed that the four-lncRNA signature was an independent prognostic biomarker after adjusting for other clinicopathologic factors. Moreover, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the immune response and cellular metabolism were significantly associated with the four-lncRNA risk signature. Conclusion: Taken together, the four-lncRNA risk signature was identified as a novel prognostic marker for IDH mutant glioma patients and may potentially lead to improvements in the lives of glioma patients.

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