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低级别弥漫性神经胶质瘤中可变剪接事件的特征及预后意义。

Characterization and prognostic significance of alternative splicing events in lower-grade diffuse gliomas.

机构信息

Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

出版信息

J Cell Mol Med. 2020 Nov;24(22):13171-13180. doi: 10.1111/jcmm.15924. Epub 2020 Oct 2.

Abstract

Alternative splicing (AS) is assumed to play important roles in the progression and prognosis of cancer. Currently, the comprehensive analysis and clinical relevance of AS in lower-grade diffuse gliomas have not been systematically addressed. Here, we gathered alternative splicing data of lower-grade diffuse gliomas from SpliceSeq. Based on the Percent Spliced In (PSI) values of 515 lower-grade diffuse glioma patients from the Cancer Genome Atlas (TCGA), we performed subtype-differential AS analysis and consensus clustering to determine robust clusters of patients. A total of 48 050 AS events in 10 787 genes in lower-grade diffuse gliomas were profiled. Subtype-differential splicing analysis and functional annotation revealed that spliced genes were significantly enriched in numerous cancer-related biological phenotypes and signalling pathways. Consensus clustering using AS events identified three robust clusters of patients with distinguished pathological and prognostic features. Moreover, each cluster was also associated with distinct genomic alterations. Finally, we developed and validated an AS-related signature with Cox proportional hazards model. The signature, significantly associated with clinical and molecular features, could serve as an independent prognostic factor for lower-grade diffuse gliomas. Thus, our results indicated that AS events could discriminate molecular subtypes and have prognostic impact in lower-grade diffuse gliomas.

摘要

选择性剪接(AS)被认为在癌症的发生和预后中起着重要作用。目前,尚未系统地研究低级别弥漫性神经胶质瘤中 AS 的综合分析和临床相关性。在这里,我们从 SpliceSeq 收集了低级别弥漫性神经胶质瘤的选择性剪接数据。基于癌症基因组图谱(TCGA)中 515 名低级别弥漫性神经胶质瘤患者的 Percent Spliced In(PSI)值,我们进行了亚型差异 AS 分析和共识聚类,以确定具有稳健特征的患者聚类。总共在 10,787 个基因中鉴定出了低级别弥漫性神经胶质瘤中的 48,050 个 AS 事件。亚型差异剪接分析和功能注释表明,剪接基因在许多与癌症相关的生物学表型和信号通路中显著富集。使用 AS 事件进行的共识聚类确定了具有明显病理和预后特征的三个稳健的患者聚类。此外,每个聚类还与不同的基因组改变相关。最后,我们使用 Cox 比例风险模型开发并验证了一个与 AS 相关的特征。该特征与临床和分子特征显著相关,可作为低级别弥漫性神经胶质瘤的独立预后因素。因此,我们的研究结果表明,AS 事件可以区分分子亚型,并对低级别弥漫性神经胶质瘤具有预后影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e04/7701518/ca2eb25ab7d8/JCMM-24-13171-g001.jpg

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本文引用的文献

1
Molecular subtyping reveals immune alterations in IDH wild-type lower-grade diffuse glioma.
J Pathol. 2020 Jul;251(3):272-283. doi: 10.1002/path.5468. Epub 2020 Jun 15.
2
Classification of diffuse lower-grade glioma based on immunological profiling.
Mol Oncol. 2020 Sep;14(9):2081-2095. doi: 10.1002/1878-0261.12707. Epub 2020 Jun 5.
3
Prognostic power of a lipid metabolism gene panel for diffuse gliomas.
J Cell Mol Med. 2019 Nov;23(11):7741-7748. doi: 10.1111/jcmm.14647. Epub 2019 Sep 1.
4
Molecular classification of IDH-mutant glioblastomas based on gene expression profiles.
Carcinogenesis. 2019 Jul 20;40(7):853-860. doi: 10.1093/carcin/bgz032.
5
Identification of an energy metabolism-related signature associated with clinical prognosis in diffuse glioma.
Aging (Albany NY). 2018 Nov 8;10(11):3185-3209. doi: 10.18632/aging.101625.
6
Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor.
Cell. 2018 Nov 29;175(6):1665-1678.e18. doi: 10.1016/j.cell.2018.09.038. Epub 2018 Oct 18.
7
Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients.
Cancer Cell. 2018 Aug 13;34(2):211-224.e6. doi: 10.1016/j.ccell.2018.07.001. Epub 2018 Aug 2.
8
Prognostic Signature of Alternative Splicing Events in Bladder Urothelial Carcinoma Based on Spliceseq Data from 317 Cases.
Cell Physiol Biochem. 2018;48(3):1355-1368. doi: 10.1159/000492094. Epub 2018 Jul 26.
9
Transcriptome-Wide Analysis Reveals the Landscape of Aberrant Alternative Splicing Events in Liver Cancer.
Hepatology. 2019 Jan;69(1):359-375. doi: 10.1002/hep.30158. Epub 2018 Dec 18.
10
CDK5 Inhibition Resolves PKA/cAMP-Independent Activation of CREB1 Signaling in Glioma Stem Cells.
Cell Rep. 2018 May 8;23(6):1651-1664. doi: 10.1016/j.celrep.2018.04.016.

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