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.
肺腺癌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的选择性剪接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具有重要贡献。近期多组学研究揭示了从发生到转移过程中肺腺癌肿瘤发生的剪接谱特征。这一进展为开发筛查策略和个体化治疗方案提供了有力前景。异常的选择性剪接促进了新抗原资源的产生和免疫微环境的紊乱，这为探索肺腺癌免疫治疗的调控靶点提供了新的研究方向。本综述系统阐述了肺腺癌中异常剪接事件的现状、相关机制及诊疗前景，特别聚焦于基于选择性剪接的免疫治疗策略（如嵌合抗原受体T细胞疗法）。这些选择性剪接变异体可与现有肺腺癌治疗模块联合应用，推动从基础研究到临床实践的转化，以应对这种高度恶性癌症的挑战。
Alternative Splicing in Lung Adenocarcinoma: From Bench to Bedside
肿瘤(癌症)患者之家