Xu Mingxin, Liu Wenwen, Zou Kun, Wei Song, Zhang Xinri, Li Encheng, Wang Qi
Department of Respiratory Medicine, The Second Hospital Affiliated to Dalian Medical University, No. 467 Zhongshan Road, Dalian 116023, China.
Cancer Translational Medicine Research Center, The Second Hospital Affiliated to Dalian Medical University, No. 467 Zhongshan Road, Dalian 116023, China.
Micromachines (Basel). 2021 Jan 2;12(1):49. doi: 10.3390/mi12010049.
Circulating tumor cells (CTCs) have been considered as an alternative to tissue biopsy for providing both germline-specific and tumor-derived genetic variations. Single-cell analysis of CTCs enables in-depth investigation of tumor heterogeneity and individualized clinical assessment. However, common CTC enrichment techniques generally have limitations of low throughput and cell damage. Herein, based on micropore-arrayed filtration membrane and microfluidic chip, we established an integrated CTC isolation platform with high-throughput, high-efficiency, and less cell damage. We observed a capture rate of around 85% and a purity of 60.4% by spiking tumor cells (PC-9) into healthy blood samples. Detection of CTCs from lung cancer patients demonstrated a positive detectable rate of 87.5%. Additionally, single CTCs, ctDNA and liver biopsy tissue of a representative advanced lung cancer patient were collected and sequenced, which revealed comprehensive genetic information of CTCs while reflected the differences in genetic profiles between different biological samples. This work provides a promising tool for CTCs isolation and further analysis at single-cell resolution with potential clinical value.
循环肿瘤细胞（CTCs）已被视为组织活检的替代方法，可提供种系特异性和肿瘤衍生的基因变异。对CTCs进行单细胞分析能够深入研究肿瘤异质性并进行个体化临床评估。然而，常见的CTCs富集技术通常存在通量低和细胞损伤的局限性。在此，基于微孔阵列过滤膜和微流控芯片，我们建立了一个具有高通量、高效率且细胞损伤少的集成CTCs分离平台。通过将肿瘤细胞（PC-9）掺入健康血液样本中，我们观察到捕获率约为85%，纯度为60.4%。对肺癌患者的CTCs检测显示阳性可检测率为87.5%。此外，收集并测序了一名代表性晚期肺癌患者的单个CTCs、ctDNA和肝活检组织，这揭示了CTCs的全面遗传信息，同时反映了不同生物样本之间基因谱的差异。这项工作为以单细胞分辨率分离CTCs并进行进一步分析提供了一个有前景的工具，具有潜在的临床价值。
