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Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma
BACKGROUND: 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. However, the expression and clinical prognostic value of antisense lncRNAs in diffuse glioma patients...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064140/ https://www.ncbi.nlm.nih.gov/pubmed/30069164 http://dx.doi.org/10.1186/s12935-018-0603-2 |
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author | Wu, Fan Zhao, Zheng Chai, Ruichao Liu, Yuqing Wang, Kuanyu Wang, Zhiliang Li, Guanzhang Huang, Ruoyu Jiang, Haoyu Zhang, Kenan |
author_facet | Wu, Fan Zhao, Zheng Chai, Ruichao Liu, Yuqing Wang, Kuanyu Wang, Zhiliang Li, Guanzhang Huang, Ruoyu Jiang, Haoyu Zhang, Kenan |
author_sort | Wu, Fan |
collection | PubMed |
description | BACKGROUND: 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. However, the expression and clinical prognostic value of antisense lncRNAs in diffuse glioma patients remain unknown. METHODS: Here, 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. RESULTS: Expression 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. CONCLUSION: Our findings provided convincing evidence that WDFY3-AS2 is a novel valuable prognostic biomarker for diffuse glioma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-018-0603-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6064140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60641402018-08-01 Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma Wu, Fan Zhao, Zheng Chai, Ruichao Liu, Yuqing Wang, Kuanyu Wang, Zhiliang Li, Guanzhang Huang, Ruoyu Jiang, Haoyu Zhang, Kenan Cancer Cell Int Primary Research BACKGROUND: 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. However, the expression and clinical prognostic value of antisense lncRNAs in diffuse glioma patients remain unknown. METHODS: Here, 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. RESULTS: Expression 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. CONCLUSION: Our findings provided convincing evidence that WDFY3-AS2 is a novel valuable prognostic biomarker for diffuse glioma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-018-0603-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-28 /pmc/articles/PMC6064140/ /pubmed/30069164 http://dx.doi.org/10.1186/s12935-018-0603-2 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Primary Research Wu, Fan Zhao, Zheng Chai, Ruichao Liu, Yuqing Wang, Kuanyu Wang, Zhiliang Li, Guanzhang Huang, Ruoyu Jiang, Haoyu Zhang, Kenan Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma |
title | Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma |
title_full | Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma |
title_fullStr | Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma |
title_full_unstemmed | Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma |
title_short | Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma |
title_sort | expression profile analysis of antisense long non-coding rna identifies wdfy3-as2 as a prognostic biomarker in diffuse glioma |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064140/ https://www.ncbi.nlm.nih.gov/pubmed/30069164 http://dx.doi.org/10.1186/s12935-018-0603-2 |
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