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肺腺癌中的可变剪接:从基础到临床

英文原题:Alternative Splicing in Lung Adenocarcinoma: From Bench to Bedside.

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Alternative Splicing in Lung Adenocarcinoma: From Bench to Bedside.

PubMed 2025/04/15(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

肺腺癌(LUAD)是一种高度异质性的肿瘤,也是肺癌中最常见的病理类型。mRNA的可变剪接(AS)使得单个基因能够产生多种蛋白质产物。这是一个受到严格调控的过程,对真核生物蛋白质组的多样性有重要贡献。近年来的多组学研究已经描绘了LUAD从发生到转移过程中肿瘤发生的剪接图谱。这些进展为促进筛查策略和个体化治疗的开发提供了坚实的希望。AS的紊乱促进了新抗原资源的出现和免疫微环境的扰动,这为LUAD免疫治疗的调控靶点提供了新的研究方向。本综述更新了LUAD中失调剪接事件的全景图及相关机制和诊疗视角,并对基于AS的免疫治疗(如CAR-T 细胞疗法)提供了独特见解。这些AS变异体可与LUAD当前的治疗模块联合使用,实现从基础到临床的转化,以对抗这种高度恶性的癌症。

展开英文摘要原文

Lung adenocarcinoma (LUAD) is a highly heterogeneous tumor and the most prevalent pathological type of lung cancer. The alternative splicing (AS) of mRNA enables the generation of multiple protein products from a single gene. This is a tightly regulated process that significantly contributes to the proteome diversity in eukaryotes. Recent multi-omics studies have delineated the splicing profiles that underline LUAD tumorigenesis from initiation to metastasis. Such progress holds robust promise to facilitate the development of screening strategies and individualized therapies.

Perturbed AS fosters the emergence of novel neoantigen resources and disturbances in the immune microenvironment, which allow new investigations into modulatory targets for LUAD immunotherapy.

This review presents an update on the landscape of dysregulated splicing events in LUAD and the associated mechanisms and theranostic perspectives with unique insights into AS-based immunotherapy, such as Chimeric Antigen Receptor T cell therapy. These AS variants can be used in conjunction with current therapeutic modules in LUAD, allowing bench to bedside translation to combat this highly malignant cancer.

论文信息

作者
Luo W、Xu M、Wong N、Ng CS
单位
Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.United Kingdom
文献类型
综述
期刊
Cancers2025 Apr 15
原文标识
PubMed 40282505 · DOI 10.3390/cancers17081329