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基于大规模低级别胶质瘤队列的预后相关 mRNA 可变剪接景观和新型剪接因子的全基因组分析。

Genome-wide analyses of the prognosis-related mRNA alternative splicing landscape and novel splicing factors based on large-scale low grade glioma cohort.

机构信息

Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi 533000, China.

Clinical College of Youjiang Medical University for Nationalities, Baise 533000, China.

出版信息

Aging (Albany NY). 2020 Jul 13;12(13):13684-13700. doi: 10.18632/aging.103491.

DOI:10.18632/aging.103491
PMID:32658870
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7377828/
Abstract

Alternative splicing (AS) changes are considered to be critical in predicting treatment response. Our study aimed to investigate differential splicing patterns and to elucidate the role of splicing factor (SF) as prognostic markers of low-grade glioma (LGG). We downloaded RNA-seq data from a cohort of 516 LGG tumors in The Cancer Genome Atlas and analyzed independent prognostic factors using LASSO regression and Cox proportional regression to build a network based on the correlation between SF-related survival AS events. We collected 100 patients from our center for immunohistochemistry and analyzed survival using χ2 test and Cox and Kaplan-Meier analyses. A total of 9,616 AS events related to LGG were screened and identified as well as established related models. Through analyzing specific splicing patterns in LGG, we screened 16 genes to construct a prognostic model to stratify the risk of LGG patients. Validation revealed that the expression level of the prognostic model in LGG tissue was increased, and patients with high expression showed worse prognosis. In summary, we demonstrated the role of SFs and AS events in the progression of LGG, which may provide insights into the clinical significance and aid the future exploration of LGG-associated AS.

摘要

可变剪接 (AS) 变化被认为是预测治疗反应的关键。我们的研究旨在调查差异剪接模式,并阐明剪接因子 (SF) 作为低级别胶质瘤 (LGG) 预后标志物的作用。我们从癌症基因组图谱中的 516 个 LGG 肿瘤队列中下载了 RNA-seq 数据,并使用 LASSO 回归和 Cox 比例回归分析独立的预后因素,以构建基于 SF 相关生存 AS 事件之间相关性的网络。我们从我们的中心收集了 100 名患者进行免疫组织化学分析,并使用 χ2 检验、Cox 和 Kaplan-Meier 分析来分析生存情况。总共筛选出 9616 个与 LGG 相关的 AS 事件,并建立了相关模型。通过分析 LGG 中的特定剪接模式,我们筛选出 16 个基因来构建预后模型,以对 LGG 患者的风险进行分层。验证结果表明,LGG 组织中预后模型的表达水平增加,高表达的患者预后较差。总之,我们证明了 SF 和 AS 事件在 LGG 进展中的作用,这可能为临床意义提供了新的认识,并有助于未来对 LGG 相关 AS 的探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/788fd4f88368/aging-12-103491-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/efde85d4f659/aging-12-103491-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/8053dc22d347/aging-12-103491-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/103b27668412/aging-12-103491-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/a009744cda13/aging-12-103491-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/b9465207ab7c/aging-12-103491-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/0ffe68059e04/aging-12-103491-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/a80330911052/aging-12-103491-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/788fd4f88368/aging-12-103491-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/efde85d4f659/aging-12-103491-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/8053dc22d347/aging-12-103491-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/103b27668412/aging-12-103491-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/a009744cda13/aging-12-103491-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/b9465207ab7c/aging-12-103491-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/0ffe68059e04/aging-12-103491-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/7377828/788fd4f88368/aging-12-103491-g008.jpg

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