在全基因组范围内鉴定 9 种癌症的泛癌症常见和癌症特异性替代剪接事件。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-08-13 DOI:10.1016/j.ygeno.2024.110917
Kun Li , Chao Cheng , Qianling Piao , Qi Zhao , Jingwen Yi , Yongli Bao , Lei Liu , Luguo Sun
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引用次数: 0

摘要

交替剪接(AS)与癌症有重要的临床意义,是新表位的潜在来源。在这项研究中,我们使用自己开发的 SUVA 对来自 47 名临床患者的 94 个实体瘤和匹配的邻近正常组织(涵盖 9 种癌症类型)的 RNA-seq 数据进行了全面分析。结果发现了一系列肿瘤样本中高度保守的泛癌症差异替代剪接(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)与常见癌症相关DAS之间的共扰网络,提示了差异表达的SFs对DAS调控的潜在可能性。最后,利用 TCGA 数据集对常见的癌症相关 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。简而言之,我们的研究阐明了癌症中保守和特异性DAS的新见解,为癌症治疗靶点提供了宝贵的资源。
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Genome-wide identification of pan-cancer common and cancer-specific alternative splicing events in 9 types of cancer

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.

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