AS-CMC: a pan-cancer database of alternative splicing for molecular classification of cancer.
AS-CMC: a pan-cancer database of alternative splicing for molecular classification of cancer.
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DOI：
10.1038/s41598-022-25584-6
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发表时间：
2022-12-06
影响因子：
4.6
通讯作者：
Chung, Yeun-Jun
中科院分区：
文献类型：
--
作者：
Park, Jiyeon;Lee, Jin-Ok;Lee, Minho;Chung, Yeun-Jun
选择性剪接（AS）是一种转录后调控，导致转录组的复杂性。尽管AS在癌症研究中的重要性日益增加，但AS的作用尚未得到系统研究，特别是在理解癌症分子分类方面。在此，我们分析了分子亚型特异性调节AS使用癌症基因组图谱数据，并构建了一个基于Web的数据库，命名为癌症分子分类的选择性剪接（AS-CMC）。我们的系统包含三个分析模块，用于探索亚型特异性AS事件，评估其表型相关性，并进行泛癌症比较。发现亚型特异性AS事件的数量在癌症类型中是不同的，并且在多种癌症类型中反复发现一些差异调节的AS事件。我们分析了丝裂原活化蛋白激酶激酶7（MAP 3 K7）外显子11中的亚型特异性AS，作为泛癌AS生物标志物的一个例子。该AS标记物与胃腺癌患者的生存率显著相关。我们的分析显示AS是癌症分子分类的重要决定因素。AS-CMC是第一个基于网络的资源，提供了一个全面的工具，探索AS事件的生物学意义，促进新的AS生物标志物的发现。
Alternative splicing (AS) is a post-transcriptional regulation that leads to the complexity of the transcriptome. Despite the growing importance of AS in cancer research, the role of AS has not been systematically studied, especially in understanding cancer molecular classification. Herein, we analyzed the molecular subtype-specific regulation of AS using The Cancer Genome Atlas data and constructed a web-based database, named Alternative Splicing for Cancer Molecular Classification (AS-CMC). Our system harbors three analysis modules for exploring subtype-specific AS events, evaluating their phenotype association, and performing pan-cancer comparison. The number of subtype-specific AS events was found to be diverse across cancer types, and some differentially regulated AS events were recurrently found in multiple cancer types. We analyzed a subtype-specific AS in exon 11 of mitogen-activated protein kinase kinase 7 (MAP3K7) as an example of a pan-cancer AS biomarker. This AS marker showed significant association with the survival of patients with stomach adenocarcinoma. Our analysis revealed AS as an important determinant for cancer molecular classification. AS-CMC is the first web-based resource that provides a comprehensive tool to explore the biological implications of AS events, facilitating the discovery of novel AS biomarkers.
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