The systematic identification of survival-related alternative splicing events and splicing factors in glioblastoma

IF 1 4区生物学 Q4 GENETICS & HEREDITY

Annals of Human Genetics Pub Date : 2024-02-19 DOI:10.1111/ahg.12550

Tao Peng, Zhe Liu, Yu Zhang, Xudong Liu, Lijun Zhao, Ying Ma, Jinke Fan, Xinqiang Song, Lei Wang

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引用次数: 0

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, making it one of the most life-threatening human cancers. Nevertheless, research on the mechanism of action between alternative splicing (AS) and splicing factor (SF) or biomarkers in GBM is limited. AS is a crucial post-transcriptional regulatory mechanism. More than 95% of human genes undergo AS events. AS can diversify the expression patterns of genes, thereby increasing the diversity of proteins and playing a significant role in the occurrence and development of tumors. In this study, we downloaded 599 clinical data and 169 transcriptome analysis data from The Cancer Genome Atlas (TCGA) database. Besides, we collected AS data about GBM from TCGA-SpliceSeq. The overall survival (OS) related AS events in GBM were determined through least absolute shrinkage and selection operator (Lasso) and Cox analysis. Subsequently, the association of these 1825 OS-related AS events with patient survival was validated using the Kaplan–Meier survival analysis, receiver operating characteristic curve, risk curve analysis, and independent prognostic analysis. Finally, we depicted the AS–SF regulatory network, illustrating the interactions between splicing factors and various AS events in GBM. Additionally, we identified three splicing factors (RNU4-1, SEC31B, and CLK1) associated with patient survival. In conclusion, based on AS occurrences, we developed a predictive risk model and constructed an interaction network between GBM-related AS events and SFs, aiming to shed light on the underlying mechanisms of GBM pathogenesis and progression.

查看原文本刊更多论文

系统识别胶质母细胞瘤中与生存相关的替代剪接事件和剪接因子。

多形性胶质母细胞瘤（GBM）是最常见、最具侵袭性的原发性脑肿瘤，也是最危及生命的人类癌症之一。然而，有关替代剪接（AS）和剪接因子（SF）或生物标志物在多形性胶质母细胞瘤中的作用机制的研究还很有限。AS是一种重要的转录后调控机制。95%以上的人类基因都经历过AS事件。AS能使基因的表达模式多样化，从而增加蛋白质的多样性，并在肿瘤的发生和发展中发挥重要作用。本研究从癌症基因组图谱（TCGA）数据库中下载了599个临床数据和169个转录组分析数据。此外，我们还从TCGA-SpliceSeq中收集了有关GBM的AS数据。通过最小绝对缩小和选择算子（Lasso）和Cox分析，确定了GBM中与总生存（OS）相关的AS事件。随后，通过卡普兰-梅耶尔生存分析、接收者操作特征曲线、风险曲线分析和独立预后分析，验证了这1825例与OS相关的AS事件与患者生存的关联性。最后，我们描绘了 AS-SF 调控网络，说明了剪接因子与 GBM 中各种 AS 事件之间的相互作用。此外，我们还发现了三个与患者生存相关的剪接因子（RNU4-1、SEC31B 和 CLK1）。总之，根据AS的发生率，我们建立了一个预测风险模型，并构建了GBM相关AS事件与SF之间的相互作用网络，旨在揭示GBM发病和进展的内在机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Human Genetics 生物-遗传学

CiteScore

4.20

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Annals of Human Genetics publishes material directly concerned with human genetics or the application of scientific principles and techniques to any aspect of human inheritance. Papers that describe work on other species that may be relevant to human genetics will also be considered. Mathematical models should include examples of application to data where possible. Authors are welcome to submit Supporting Information, such as data sets or additional figures or tables, that will not be published in the print edition of the journal, but which will be viewable via the online edition and stored on the website.