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基于转录组的结直肠癌相关可变剪接分析。

Analysis of Colorectal Cancer-Associated Alternative Splicing Based on Transcriptome.

机构信息

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, P.R. China.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, P.R. China.

出版信息

DNA Cell Biol. 2020 Jan;39(1):16-24. doi: 10.1089/dna.2019.5111. Epub 2019 Dec 5.

Abstract

Colorectal cancer (CRC) is a severe risk to public health, and there is growing evidence that alternative splicing (AS) plays a crucial role in cancer. However, the AS biomarkers in CRC are seldom reported. In this study, we perform transcriptome analysis of colorectal samples for cancer-specific AS and transcriptomic alterations. We identify 1577 splice events in 885 genes, enriched in CRC-associated pathways and functions. In parallel, we find 10 splicing factors (SFs) with transcriptome variation or significant differential expression. Based on co-expression and binding motif, we construct an SF-AS regulatory network, revealing the association between cancer-specific AS and aberrant SF. Integrating The Cancer Genome Atlas and published sources, we observed that some recurrent AS is an indicator of poor prognosis. Through further experimental verification, we found that the AS of six genes showed significant differences between the tumor sample and the normal sample, and AS of and can be used as new potential biomarkers in CRC. Our study provides an important analysis of CRC-associated AS, which could act as a starting point for future functional explorations, the development of biomarkers and AS-based target therapy.

摘要

结直肠癌(CRC)严重威胁公众健康,越来越多的证据表明选择性剪接(AS)在癌症中起着关键作用。然而,CRC 中的 AS 生物标志物很少被报道。在这项研究中,我们对结直肠样本进行了转录组分析,以研究癌症特异性 AS 和转录组改变。我们在 885 个基因中鉴定出 1577 个剪接事件,这些事件富集在与 CRC 相关的途径和功能中。同时,我们发现了 10 个剪接因子(SFs)具有转录组变化或显著差异表达。基于共表达和结合基序,我们构建了一个 SF-AS 调控网络,揭示了癌症特异性 AS 与异常 SF 之间的关联。整合癌症基因组图谱和已发表的资料,我们观察到一些反复出现的 AS 是预后不良的标志。通过进一步的实验验证,我们发现六个基因的 AS 在肿瘤样本和正常样本之间存在显著差异,并且和 可以作为 CRC 中的新的潜在生物标志物。我们的研究为 CRC 相关 AS 提供了重要的分析,这可能成为未来功能探索、生物标志物开发和基于 AS 的靶向治疗的起点。

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