Abstract
BackgroundIncreasing evidence has shown that long non-coding RNAs (lncRNAs) are important prognostic biomarkers and epigenetic regulators with critical roles in cancer initiation and progression. However, the expression and clinical prognostic value of antisense lncRNAs in diffuse glioma patients remain unknown.MethodsHere, we profiled differentially expressed antisense lncRNAs in glioma using RNA sequencing data from Chinese Glioma Genome Atlas database. Cox regression was performed to evaluate the prognostic value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were used for functional analysis of antisense LncRNAs.ResultsExpression profiling identified 169 aberrantly expressed antisense lncRNAs between lower grade glioma (LGG) (grade II and III) and glioblastoma multiforme (GBM), 113 antisense lncRNAs between LGG IDH-wt and IDH-mut samples, and 70 antisense lncRNAs between GBM IDH-wt and IDH-mut samples, respectively. Among them, three antisense lncRNAs (WDFY3-AS2, MCM3AP-AS1 and LBX2-AS1) were significantly associated with prognosis and malignant progression of patients. WDFY3-AS2, the top one of downregulated antisense lncRNAs in GBM with fold change of 0.441 (P < 0.001), showed specific decreased expression in classical, mesenchymal, LGG IDH-wt, GBM IDH-wt or MGMT promoter unmethylated stratified patients. Chi square test found that WDFY3-AS2 was significantly associated with the clinical and molecular features of glioma. Univariate and multivariate Cox regression analysis indicated that WDFY3-AS2 was independently correlated with overall survival (OS) of patients. Kaplan–Meier analysis found that patients with high WDFY3-AS2 expression had longer OS than the low expression ones in the stratified cohorts. Additionally, GO and GSEA showed that gene sets correlated with WDFY3-AS2 expression were involved in regulation of synaptic transmission, glutamate receptor and TNF signaling pathway.ConclusionOur findings provided convincing evidence that WDFY3-AS2 is a novel valuable prognostic biomarker for diffuse glioma.
Highlights
Increasing evidence has shown that long non-coding RNAs are important prognostic biomarkers and epigenetic regulators with critical roles in cancer initiation and progression
70 antisense long non-coding RNAs (lncRNAs) were downregulated in Glioblastoma multiforme (GBM) samples compared with lower grade glioma (LGG) samples, while 99 antisense lncRNAs were upregulated in GBM samples
Hierarchical clustering analysis conducted with R package “pheatmap” showed systematic variations in expression of these 169 antisense lncRNAs among samples (Fig. 1d)
Summary
Increasing evidence has shown that long non-coding RNAs (lncRNAs) are important prognostic biomarkers and epigenetic regulators with critical roles in cancer initiation and progression. The expression and clinical prognostic value of antisense lncRNAs in diffuse glioma patients remain unknown. Accumulating reports found that dysregulated expression of antisense lncRNAs plays a crucial role in development and progression of various cancers. Zhu et al found that upregulation of lncRNA ZEB1-AS1 promoted tumor metastasis and predicted poor prognosis in hepatocellular carcinoma [9]. Our previous study reported that upregulation of lncRNA HOXA-AS3 promoted tumor progression and predicted poor prognosis in glioma [12]. Understanding the role and prognostic value of cancer associated antisense lncRNAs would reveal new perspectives on the molecular basis of gliomagenesis
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