机构:[1]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.研究所北京市神经外科研究所首都医科大学附属天坛医院[2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[3]Chinese Glioma Genome Atlas Network (CGGA) and Asian Glioma Genome Atlas Network (AGGA), Beijing, China.[4]No. 6, Tiantan Xili, Dongcheng District, Beijing 100050, China
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 IncRNAs between lower grade glioma (LGG) (grade II and III) and glioblastoma multiforme (GBM), 113 antisense IncRNAs between LGG IDH-wt and IDHmut samples, and 70 antisense IncRNAs between GBM IDH-wt and IDH-mut samples, respectively. Among them, three antisense IncRNAs (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 IncRNAs 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.
基金:
National Natural Science Foundation of China (NSFC)/Research Grants Council (RGC) Joint Research Scheme [81761168038]; National Key Research and Development Plan [2016YFC0902500]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81672479, 81773208]
第一作者机构:[1]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.[2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.[3]Chinese Glioma Genome Atlas Network (CGGA) and Asian Glioma Genome Atlas Network (AGGA), Beijing, China.[4]No. 6, Tiantan Xili, Dongcheng District, Beijing 100050, China
共同第一作者:
通讯作者:
通讯机构:[1]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.[2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.[3]Chinese Glioma Genome Atlas Network (CGGA) and Asian Glioma Genome Atlas Network (AGGA), Beijing, China.[4]No. 6, Tiantan Xili, Dongcheng District, Beijing 100050, China
推荐引用方式(GB/T 7714):
Fan Wu,Zheng Zhao,Ruichao Chai,et al.Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma[J].CANCER CELL INTERNATIONAL.2018,18(1):-.doi:10.1186/s12935-018-0603-2.
APA:
Fan Wu,Zheng Zhao,Ruichao Chai,Yuqing Liu,Kuanyu Wang...&Kenan Zhang.(2018).Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma.CANCER CELL INTERNATIONAL,18,(1)
MLA:
Fan Wu,et al."Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma".CANCER CELL INTERNATIONAL 18..1(2018):-