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可变剪接事件在头颈部鳞状细胞癌中的预后作用

Prognostic role of alternative splicing events in head and neck squamous cell carcinoma.

作者信息

Ding Yanni, Feng Guang, Yang Min

机构信息

Department of Breast Surgery, Shaan Xi Provincial Tumor Hospital, Xi'an City, Shaan Xi Province 710000 China.

2The Third Department of Burns and Plastic Surgery and Center of Wound Repair, The Fourth Medical Center of PLA General Hospital, Beijing, 100048 China.

出版信息

Cancer Cell Int. 2020 May 14;20:168. doi: 10.1186/s12935-020-01249-0. eCollection 2020.

Abstract

BACKGROUND

Aberrant alternative splicing (AS) is implicated in biological processes of cancer. This study aims to reveal prognostic AS events and signatures that may serve as prognostic predictors for head and neck squamous cell carcinoma (HNSCC).

METHODS

Prognostic AS events in HNSCC were identified by univariate COX analysis. Prognostic signatures comprising prognostic AS events were constructed for prognosis prediction in patients with HNSCC. The correlation between the percent spliced in (PSI) values of AS events and the expression of splicing factors (SFs) was analyzed by Pearson correlation analysis. Gene functional annotation analysis was performed to reveal pathways in which prognostic AS is enriched.

RESULTS

A total of 27,611 AS events in 15,873 genes were observed, and there were 3433 AS events in 2624 genes significantly associated with overall survival (OS) for HNSCC. Moreover, we found that AS prognostic signatures could accurately predict HNSCC prognosis. SF-AS regulatory networks were constructed according to the correlation between PSI values of AS events and the expression levels of SFs.

CONCLUSIONS

Our study identified prognostic AS events and signatures. Furthermore, it established SF-AS networks in HNSCC that were valuable in predicting the prognosis of patients with HNSCC and elucidating the regulatory mechanisms underlying AS in HNSCC.

摘要

背景

异常可变剪接(AS)与癌症的生物学过程有关。本研究旨在揭示可能作为头颈部鳞状细胞癌(HNSCC)预后预测指标的预后性AS事件和特征。

方法

通过单因素COX分析确定HNSCC中的预后性AS事件。构建包含预后性AS事件的预后特征,用于预测HNSCC患者的预后。通过Pearson相关分析分析AS事件的剪接百分率(PSI)值与剪接因子(SFs)表达之间的相关性。进行基因功能注释分析以揭示预后性AS富集的途径。

结果

共观察到15873个基因中的27611个AS事件,其中2624个基因中的3433个AS事件与HNSCC的总生存期(OS)显著相关。此外,我们发现AS预后特征可以准确预测HNSCC的预后。根据AS事件的PSI值与SFs表达水平之间的相关性构建了SF-AS调控网络。

结论

我们的研究确定了预后性AS事件和特征。此外,它在HNSCC中建立了SF-AS网络,这对于预测HNSCC患者的预后以及阐明HNSCC中AS的调控机制具有重要价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdf4/7227031/8bb0425b8a04/12935_2020_1249_Fig1_HTML.jpg

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