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全面系统地鉴定膀胱癌特异的 SF 调控、生存相关的 AS 事件。

The comprehensive and systematic identification of BLCA-specific SF-regulated, survival-related AS events.

机构信息

Department of Computer Science, City University of Hong Kong, Hong Kong, China.

School of Medicine, Chongqing University, Chongqing 400044, China; Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China.

出版信息

Gene. 2022 Aug 15;835:146657. doi: 10.1016/j.gene.2022.146657. Epub 2022 Jun 13.

Abstract

Bladder urothelial carcinoma (BLCA) is a complex disease with high morbidity and mortality. Changes in alternative splicing (AS) and splicing factor (SF) can affect gene expression, thus playing an essential role in tumorigenesis. This study downloaded 412 patients' clinical information and 433 samples of transcriptome profiling data from TCGA. And we collected 48 AS signatures from SpliceSeq. LASSO and Cox analyses were used for identifying survival-related AS events in BLCA. Finally, 1,645 OS-related AS events in 1,129 genes were validated by Kaplan-Meier (KM) survival analysis, ROC analysis, risk curve analysis, and independent prognostic analysis. Finally, our survey provides an AS-SF regulation network consisting of five SFs and 46 AS events. In the end, we profiled genes that AS occurred in pan-cancer and five SFs' expression in tumor and normal samples in BLCA. We selected CLIP-seq data for validation the interaction regulated by RBP. Our study paves the way for potential therapeutic targets of BLCA.

摘要

膀胱癌(BLCA)是一种发病率和死亡率都很高的复杂疾病。可变剪接(AS)和剪接因子(SF)的改变会影响基因表达,从而在肿瘤发生中发挥重要作用。本研究从 TCGA 下载了 412 名患者的临床信息和 433 份转录组谱数据样本,并从 SpliceSeq 中收集了 48 个 AS 特征。LASSO 和 Cox 分析用于识别 BLCA 中与生存相关的 AS 事件。最后,通过 Kaplan-Meier(KM)生存分析、ROC 分析、风险曲线分析和独立预后分析,验证了 1129 个基因中 1645 个与 OS 相关的 AS 事件。最终,我们的调查提供了一个由五个 SF 和 46 个 AS 事件组成的 AS-SF 调控网络。最后,我们在 BLCA 中对泛癌中发生 AS 的基因和五个 SF 的表达进行了肿瘤和正常样本的分析。我们选择了 CLIP-seq 数据来验证 RBP 调控的相互作用。我们的研究为 BLCA 的潜在治疗靶点铺平了道路。

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