循环肿瘤细胞检测在常见恶性肿瘤精准医学中的应用和展望

doi:10.16150/j.1671-2870.2023.04.002

摘要/Abstract

摘要：

恶性肿瘤严重威胁着人类健康。循环肿瘤细胞（circulating tumor cell, CTC）作为液体活检的分子标志物，具有微创、可实时动态监测肿瘤进展与疗效的优势。CTC的体外富集检测方法分为基于分子特征和物理特征2种。近年来发展了一系列针对不同分子特征的CTC综合富集方法，以及使用相差富集整合荧光原位杂交（subtraction enrichment and immunostaining-fluorescence in situ hybridization, SE-iFISH）进行胃癌CTC的富集检测。微流控技术可同时基于CTC的分子特征及物理特征，将其在同一芯片上进行分离富集，有助于实现更高效、灵敏的CTC富集检测。与体外CTC富集平台相比，体内CTC富集平台捕获效率和检测灵敏度更高，但为侵入性检查，对患者的影响仍需进一步研究。CTC水平高与胃癌化疗后的疾病控制率密切相关，是胃癌患者预后不良的独立预测因子。在无转移性恶性肿瘤中，食管癌及结直肠癌患者术后，单位体积CTC计数的增加与更差的总生存率密切相关。CTC具有高度异质性，动态监测CTC变化，可为恶性肿瘤的治疗提供参考依据。针对胃癌的研究发现，CTC的阳性率、细胞簇大小和基因水平，与侵袭转移能力、耐药性及患者预后密切相关，CTC的动态转移过程及模式在肿瘤的转移中起重要作用。CTC的检测，需建立统一行业标准及验证方法，发展多组学研究技术。

关键词: 循环肿瘤细胞, 胃癌, 治疗耐药监测, 预后监测, 靶向治疗

Abstract:

Malignant tumors seriously threat the health of the Chinese population. Circulating tumor cell (CTC), as molecular markers in liquid biopsy, have the advantage of being non-invasive and longitudinal monitoring of tumor progression and efficacy. In vitro CTC enrichment detection methods are divided into two types: based on molecular characteristics and based on physical characteristics. In recent years, a series of comprehensive CTC enrichment methods targeting different molecular characteristics have been developed, as well as the use of subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) for enrichment detection of gastric cancer CTC. Microfluidic technology can separate and enrich CTC on the same chip based on their molecular and physical characteristics simultaneously, helping to achieve more efficient and sensitive CTC enrichment detection. Compared with the in vitro CTC enrichment platform, the in vivo CTC enrichment platform has higher capture efficiency and detection sensitivity, but it is an invasive examination, and the impact on patients still needs further study. High CTC level is closely related to the disease control rate after gastric cancer chemotherapy and is an independent predictor of poor prognosis in gastric cancer patients. Among non-metastatic malignancies, increased CTC counts after surgery in patients with esophageal cancer and colorectal cancer are strongly associated with worse overall survival. Since CTC are highly heterogeneous, changes in CTC can be longitudinally monitored to provide a reference for the treatment of malignant tumors. Research on gastric cancer has shown that the positivity rate, size of circulating tumor microemboli (CTM) and gene expression level of CTC are closely related to the ability of invasion, metastasis, drug resistance and prognosis. The dynamic metastasis process and pattern of CTC play an important role in tumor metastasis. For the detection of CTC, it is necessary to establish unified standards and verification methods, and develop multi-omics research technology.

Key words: Circulating tumor cell, Gastric cancer, Therapeutical resistance monitoring, Prognostic monitoring, Targeted therapy

中图分类号:

李一林, 陈杨, 李艳艳, 冯旭娇, 章程, 李健, 沈琳. 循环肿瘤细胞检测在常见恶性肿瘤精准医学中的应用和展望[J]. 诊断学理论与实践, 2023, 22(04): 332-340.

LI Yilin, CHEN Yang, LI Yanyan, FENG Xujiao, ZHANG Cheng, LI Jian, SHEN Lin. Clinical application of circulating tumor cells in gastric cancer: advances and prospects[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(04): 332-340.

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