喉鳞状细胞癌中的组蛋白修饰：从表观遗传重编程到精准治疗

文献信息

中文摘要

喉鳞状细胞癌（LSCC）是头颈部常见的恶性肿瘤，占喉癌的绝大多数。其发生发展涉及遗传与表观遗传改变的复杂相互作用。组蛋白翻译后修饰作为连接细胞内代谢状态、致癌信号与转录程序的关键调控层，通过调节染色质构象、转录因子可及性和基因表达谱，参与肿瘤细胞增殖、上皮-间质转化、干性维持、代谢重编程及治疗耐药。本研究系统总结了LSCC中组蛋白乙酰化、甲基化、乳酸化及其他新型组蛋白修饰的最新进展，进一步探讨了不同组蛋白修饰之间的交互作用及其在肿瘤微环境和放疗、化疗、免疫治疗耐药中的潜在作用，并分析了靶向组蛋白修饰的治疗策略以及单细胞和空间表观基因组学在LSCC精准医学中的未来前景，旨在为LSCC生物标志物开发和表观遗传靶向治疗提供新的理论基础。

英文摘要

Laryngeal squamous cell carcinoma (LSCC) is a common malignancy of the head and neck, accounting for the vast majority of laryngeal cancers. Its development involves complex interactions between genetic and epigenetic alterations. Histone post-translational modifications, as a crucial regulatory layer linking intracellular metabolic states, oncogenic signaling, and transcriptional programs, participate in tumor cell proliferation, epithelial-mesenchymal transition, stemness maintenance, metabolic reprogramming, and therapeutic resistance by modulating chromatin conformation, transcription factor accessibility, and gene expression profiles. This study systematically summarizes recent advances in histone acetylation, methylation, lactylation, and other novel histone modifications in LSCC, further discusses crosstalk among different histone modifications and their potential roles in the tumor microenvironment and resistance to radiotherapy, chemotherapy, and immunotherapy, and analyzes therapeutic strategies targeting histone modifications as well as future prospects for single-cell and spatial epigenomics in precision medicine for LSCC, aiming to provide new theoretical foundations for biomarker development and epigenetic-targeted therapies in LSCC.