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泛癌及 9 种癌症特有剪接事件的全基因组识别。

Genome-wide identification of pan-cancer common and cancer-specific alternative splicing events in 9 types of cancer.

机构信息

National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China.

ABLife BioBigData Institute, Wuhan, China; Center for Genome Analysis, Wuhan Ruixing Biotechnology Co., Ltd., Wuhan, China.

出版信息

Genomics. 2024 Sep;116(5):110917. doi: 10.1016/j.ygeno.2024.110917. Epub 2024 Aug 13.

Abstract

Alternative splicing (AS) has significant clinical relevance with cancers and is a potential source of neoepitopes. In this study, RNA-seq data of 94 solid tumor and matched adjacent normal tissues from 47 clinical patients covering nine cancer types were comprehensively analyzed using SUVA developed by ourselves. The results identified highly conserved pan-cancer differential alternative splicing (DAS) events and cancer-specific DAS events in a series of tumor samples, which in turn revealed the heterogeneity of AS post-transcriptional regulation across different cancers. The co-disturbed network between spliceosome factors (SFs) and common cancer-associated DAS was further constructed, suggesting the potential possibility of the regulation of differentially expressed SFs on DAS. Finally, the common cancer-associated DAS events were fully validated using the TCGA dataset, confirming the significant correlation between cancer-associated DAS and prognosis. Briefly, our study elucidates new insights into conservatived and specific DAS in cancer, providing valuable resources for cancer therapeutic targets.

摘要

选择性剪接 (AS) 与癌症具有重要的临床相关性,是新表位的潜在来源。在这项研究中,我们使用自主开发的 SUVA 对来自 47 名临床患者的 94 个实体瘤和匹配的相邻正常组织的 RNA-seq 数据进行了全面分析。结果鉴定了一系列肿瘤样本中高度保守的泛癌差异剪接 (DAS) 事件和癌症特异性 DAS 事件,进而揭示了不同癌症中 AS 转录后调控的异质性。进一步构建了剪接体因子 (SFs) 和常见癌症相关 DAS 之间的共同失调网络,表明差异表达 SFs 对 DAS 进行调控的潜在可能性。最后,使用 TCGA 数据集对常见癌症相关 DAS 事件进行了全面验证,证实了癌症相关 DAS 与预后之间的显著相关性。总之,我们的研究阐明了癌症中保守和特异的 DAS 的新见解,为癌症治疗靶点提供了有价值的资源。

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