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循环肿瘤细胞的液体活检:从分离、富集、基因组测序到临床应用

Liquid biopsy of circulating tumor cells: From isolation, enrichment, and genome sequencing to clinical applications.

作者信息

Tan Keqin, Zhu Hong, Ma Xuelei

机构信息

Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

出版信息

Histol Histopathol. 2025 Apr 23:18924. doi: 10.14670/HH-18-924.

DOI:10.14670/HH-18-924
PMID:40331286
Abstract

Circulating tumor cells (CTCs), shed from primary tumors into the bloodstream, play a crucial role in metastasis and hold great potential in cancer diagnosis, prognosis, and treatment monitoring. Conventional CTC detection using epithelial biomarkers like epithelial cell adhesion molecule (EpCAM) for immunocapture overlooks mesenchymal-like CTCs with high metastatic potential, spurring the development of non-immunocapture technologies that use biophysical traits for enrichment. Innovations in microfluidic platforms and multi-parametric sorting improve isolation efficiency and address related challenges. Breakthroughs in single-cell genomic and transcriptomic sequencing enable in-depth molecular characterization of CTCs. Clinically, CTC enumeration and molecular profiling are emerging as real-time tools for assessing therapeutic response and predicting outcomes, especially in metastatic breast, prostate, and colorectal cancers. This review focuses on CTC isolation, enrichment techniques, their applications in different tumors, downstream analysis progress, and potential in precision medicine.

摘要

循环肿瘤细胞(CTCs)从原发性肿瘤脱落进入血液循环,在肿瘤转移中起关键作用,在癌症诊断、预后及治疗监测方面具有巨大潜力。使用上皮生物标志物(如上皮细胞粘附分子(EpCAM))进行免疫捕获的传统CTCs检测方法会忽略具有高转移潜力的间充质样CTCs,这促使了利用生物物理特性进行富集的非免疫捕获技术的发展。微流控平台和多参数分选技术的创新提高了分离效率并解决了相关挑战。单细胞基因组和转录组测序的突破使对CTCs进行深入分子表征成为可能。临床上,CTCs计数和分子谱分析正逐渐成为评估治疗反应和预测结果的实时工具,尤其是在转移性乳腺癌、前列腺癌和结直肠癌中。本综述重点关注CTCs的分离、富集技术、它们在不同肿瘤中的应用、下游分析进展以及在精准医学中的潜力。

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