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肺腺癌中预后替代剪接特征和剪接因子的全基因组分析。

Genome-Wide Analysis of Prognostic Alternative Splicing Signature and Splicing Factors in Lung Adenocarcinoma.

机构信息

Epigenome Research Center, China Medical University Hospital, 404 Taichung, Taiwan.

Department of Laboratory Medicine, China Medical University Hospital, 404 Taichung, Taiwan.

出版信息

Genes (Basel). 2020 Oct 31;11(11):1300. doi: 10.3390/genes11111300.

DOI:10.3390/genes11111300
PMID:33142748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7693837/
Abstract

Analysis of The Cancer Genome Atlas data revealed that alternative splicing (AS) events could serve as prognostic biomarkers in various cancer types. This study examined lung adenocarcinoma (LUAD) tissues for AS and assessed AS events as potential indicators of prognosis in our cohort. RNA sequencing and bioinformatics analysis were performed. We used SUPPA2 to analyze the AS profiles. Using univariate Cox regression analysis, overall survival (OS)-related AS events were identified. Genes relating to the OS-related AS events were imported into Cytoscape, and the CytoHubba application was run. OS-related splicing factors (SFs) were explored using the log-rank test. The relationship between the percent spliced-in value of the OS-related AS events and SF expression was identified by Spearman correlation analysis. We found 1957 OS-related AS events in 1151 genes, and most were protective factors. Alternative first exon splicing was the most frequent type of splicing event. The hub genes in the gene network of the OS-related AS events were , , , and . The area under the curve of the MIX prediction model was 0.847 for 5-year survival based on seven OS-related AS events. Overexpression of SFs and was associated with better OS. We constructed a correlation network between SFs and OS-related AS events. In conclusion, we identified prognostic predictors using AS events that stratified LUAD patients into high- and low-risk groups. The discovery of the splicing networks in this study provides an insight into the underlying mechanisms.

摘要

分析癌症基因组图谱（The Cancer Genome Atlas，TCGA）的数据显示，可变剪接（Alternative Splicing，AS）事件可以作为各种癌症类型的预后生物标志物。本研究对肺腺癌（Lung Adenocarcinoma，LUAD）组织中的 AS 进行了检测，并评估了 AS 事件作为本队列中潜在预后指标的可能性。进行了 RNA 测序和生物信息学分析。我们使用 SUPPA2 来分析 AS 谱。使用单变量 Cox 回归分析，确定了与总生存期（Overall Survival，OS）相关的 AS 事件。将与 OS 相关的 AS 事件相关的基因导入 Cytoscape，并运行 CytoHubba 应用程序。使用对数秩检验探索与 OS 相关的剪接因子（Splicing Factor，SF）。通过 Spearman 相关分析确定 OS 相关 AS 事件的插入百分比与 SF 表达之间的关系。我们在 1151 个基因中发现了 1957 个与 OS 相关的 AS 事件，且大多数为保护因子。可变外显子 1 剪接是最常见的剪接事件类型。OS 相关 AS 事件基因网络中的枢纽基因包括、、、和。基于 7 个与 OS 相关的 AS 事件，MIX 预测模型对 5 年生存率的曲线下面积为 0.847。SFs 和的过表达与更好的 OS 相关。我们构建了 SFs 和 OS 相关 AS 事件之间的相关网络。总之，我们使用 AS 事件确定了 LUAD 患者的预后预测指标，将其分为高风险和低风险组。本研究中发现的剪接网络为潜在机制提供了深入了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/a53042a56577/genes-11-01300-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/d0efb637026a/genes-11-01300-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/6357a13db090/genes-11-01300-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/0b244e93df38/genes-11-01300-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/a98c6e7edba6/genes-11-01300-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/e0bd722029d4/genes-11-01300-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/a53042a56577/genes-11-01300-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/d0efb637026a/genes-11-01300-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/6357a13db090/genes-11-01300-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/0b244e93df38/genes-11-01300-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/a98c6e7edba6/genes-11-01300-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/e0bd722029d4/genes-11-01300-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c64/7693837/a53042a56577/genes-11-01300-g006a.jpg

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[2]
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[3]
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[4]
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[5]
Identification of the Key miRNAs and Genes Associated with the Regulation of Non-Small Cell Lung Cancer: A Network-Based Approach.

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[6]
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[7]
Integrated Bioinformatics Analysis Identifies a New Stemness Index-Related Survival Model for Prognostic Prediction in Lung Adenocarcinoma.

Front Genet. 2022-4-8

[8]
CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein/Noncoding RNA Regulatory Axis.

Int J Mol Sci. 2021-10-14

[9]
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[10]
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本文引用的文献

[1]
Survival-associated alternative splicing signatures in non-small cell lung cancer.

Aging (Albany NY). 2020-4-13

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Cancers (Basel). 2018-11-20

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