循环肿瘤细胞：从新的生物学见解到临床实践
Circulating tumor cells: from new biological insights to clinical practice
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影响因子:52.7
分区:医学1区 Top / 生化与分子生物学1区 细胞生物学1区
发表日期:2024 Sep 02
作者:
Xuyu Gu, Shiyou Wei, Xin Lv
DOI:
10.1038/s41392-024-01938-6
摘要
癌症患者高死亡率的主要原因是转移，即肿瘤细胞通过血流从原发部位迁移到身体其他部位。近年来的技术进步大大增强了我们对循环肿瘤细胞（CTCs）血源性扩散机制的理解。一项关键过程是DNA甲基化，它调控基因表达和染色体稳定性，从而维持体内的动态平衡。全基因组低甲基化和位点特异性高甲基化是DNA甲基化模式变化的典型例子，在癌变过程中扮演重要角色。本综述首先概述了影响CTC形成的各种过程，包括上皮-间充质转化（EMT）、免疫监视和定殖。随后，我们深入分析了DNA甲基化修饰在CTC扩散的各个关键阶段中的作用。此外，我们探讨了DNA甲基化变化在临床上的潜在意义，包括早期检测、预后和靶向治疗的生物标志物。通过理解这些表观遗传修饰，可以深入认识转移过程并开发新的诊断和治疗策略。本综述旨在弥合基础研究与临床应用之间的差距，强调DNA甲基化在癌症转移中的重要性，并为改善患者预后提供新的研究方向。
Abstract
The primary reason for high mortality rates among cancer patients is metastasis, where tumor cells migrate through the bloodstream from the original site to other parts of the body. Recent advancements in technology have significantly enhanced our comprehension of the mechanisms behind the bloodborne spread of circulating tumor cells (CTCs). One critical process, DNA methylation, regulates gene expression and chromosome stability, thus maintaining dynamic equilibrium in the body. Global hypomethylation and locus-specific hypermethylation are examples of changes in DNA methylation patterns that are pivotal to carcinogenesis. This comprehensive review first provides an overview of the various processes that contribute to the formation of CTCs, including epithelial-mesenchymal transition (EMT), immune surveillance, and colonization. We then conduct an in-depth analysis of how modifications in DNA methylation within CTCs impact each of these critical stages during CTC dissemination. Furthermore, we explored potential clinical implications of changes in DNA methylation in CTCs for patients with cancer. By understanding these epigenetic modifications, we can gain insights into the metastatic process and identify new biomarkers for early detection, prognosis, and targeted therapies. This review aims to bridge the gap between basic research and clinical application, highlighting the significance of DNA methylation in the context of cancer metastasis and offering new avenues for improving patient outcomes.