RNA splicing junction landscape reveals abundant tumor-specific transcripts in human cancer.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2024-10-23 DOI:10.1016/j.celrep.2024.114893

Qin Li, Ziteng Li, Bing Chen, Jingjing Zhao, Hongwu Yu, Jia Hu, Hongyan Lai, Hena Zhang, Yan Li, Zhiqiang Meng, Zhixiang Hu, Shenglin Huang

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引用次数: 0

Abstract

RNA splicing is a critical process governing gene expression and transcriptomic diversity. Despite its importance, a detailed examination of transcript variation at the splicing junction level remains scarce. Here, we perform a thorough analysis of RNA splicing junctions in 34,775 samples across multiple sample types. We identified 29,051 tumor-specific transcripts (TSTs) in pan-cancer, with a majority of these TSTs being unannotated. Our findings show that TSTs are positively correlated with tumor stemness and linked to unfavorable outcomes in cancer patients. Additionally, TSTs display mutual exclusivity with somatic mutations and are overrepresented in transposable-element-derived transcripts possessing oncogenic functions. Importantly, TSTs can generate putative neoantigens for immunotherapy. Moreover, TSTs can be detected in blood extracellular vesicles from cancer patients. Our results shed light on the intricacies of RNA splicing and offer promising avenues for cancer diagnosis and therapy.

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RNA 剪接接头景观揭示了人类癌症中丰富的肿瘤特异性转录本。

RNA 剪接是控制基因表达和转录组多样性的关键过程。尽管其重要性不言而喻，但在剪接接头水平对转录本变异的详细研究仍然很少。在这里，我们对 34,775 份跨多种类型样本中的 RNA 剪接接头进行了全面分析。我们在泛癌症中发现了 29,051 个肿瘤特异性转录本（TST），其中大部分 TST 都未被标注。我们的研究结果表明，TSTs 与肿瘤干性呈正相关，并与癌症患者的不良预后有关。此外，TST 与体细胞突变具有互斥性，并且在具有致癌功能的转座元件衍生转录本中比例过高。重要的是，TST 可产生用于免疫疗法的潜在新抗原。此外，在癌症患者的血液细胞外囊泡中也能检测到 TSTs。我们的研究结果揭示了 RNA 剪接的复杂性，并为癌症诊断和治疗提供了前景广阔的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.