An Integrated Microfluidic Chip and Its Clinical Application for Circulating Tumor Cell Isolation and Single-Cell Analysis.,Cytometry Part A

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An Integrated Microfluidic Chip and Its Clinical Application for Circulating Tumor Cell Isolation and Single-Cell Analysis.
Cytometry Part A ( IF 2.5 ) Pub Date : 2019-10-09 , DOI: 10.1002/cyto.a.23902
Mingxin Xu ₁ , Hui Zhao ₁ , Jun Chen ₂ , Wenwen Liu ₁ , Encheng Li ₁ , Qi Wang ₁ , Lichuan Zhang ₃

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Circulating tumor cells (CTCs) represent invasive tumor cell populations and provide a noninvasive solution to the clinical management and research of tumors. Characterization of CTCs at single-cell resolution enables the comprehensive understanding of tumor heterogeneity and may benefit the diagnosis and treatment of cancer patients. However, most efforts have been made on enumeration and detection of CTCs, while little focus has been directed to single-cell study. Herein, an integrated microfluidic platform for single-cell isolation and analysis was established. After validating this platform on lung cancer cell lines, we detected and isolated single CTCs from the peripheral blood samples of 20 cancer patients before and after one treatment cycle. Furthermore, we performed single-cell whole-exome DNA sequencing on a single CTC from the peripheral blood sample of a representative early stage lung cancer patient. Among the blood samples of 20 patients, 15 of them were positive for CTC detection (75.0% detectable rate). Single-cell analysis revealed detailed genetic variations of the CTC, while six new gene mutations were detected in both single CTC and surgical specimen. This study provides a useful tool for the isolation and analysis of single CTCs from peripheral blood samples, which not only facilitates the early diagnosis of cancers but also helps to unravel the genetic information of tumor at a single-cell level. © 2019 International Society for Advancement of Cytometry.

中文翻译：

集成微流控芯片及其在循环肿瘤细胞分离和单细胞分析中的临床应用。

循环肿瘤细胞（CTC）代表侵入性肿瘤细胞群体，并为肿瘤的临床管理和研究提供了一种非侵入性的解决方案。以单细胞分辨率表征CTC可以全面了解肿瘤的异质性，并可能有益于癌症患者的诊断和治疗。但是，大多数工作已在CTC的枚举和检测上进行，而很少关注单细胞研究。在此，建立了用于单细胞分离和分析的集成微流体平台。在肺癌细胞系上验证该平台后，我们在一个治疗周期之前和之后从20名癌症患者的外周血样本中检测并分离了单个CTC。此外，我们对代表性的早期肺癌患者外周血样本中的单个CTC进行了单细胞全外显子组DNA测序。在20例患者的血液样本中，其中15例CTC检测呈阳性（可检出率75.0％）。单细胞分析揭示了CTC的详细遗传变异，而在单个CTC和手术标本中均检测到六个新的基因突变。这项研究为从外周血样本中分离和分析单个CTC提供了有用的工具，不仅有助于癌症的早期诊断，而且有助于在单细胞水平上揭示肿瘤的遗传信息。©2019国际细胞计数学会。其中15例CTC检测阳性（可检出率75.0％）。单细胞分析揭示了CTC的详细遗传变异，而在单个CTC和手术标本中均检测到六个新的基因突变。这项研究为从外周血样本中分离和分析单个CTC提供了有用的工具，不仅有助于癌症的早期诊断，而且有助于在单细胞水平上揭示肿瘤的遗传信息。©2019国际细胞计数学会。其中15例CTC检测阳性（可检出率75.0％）。单细胞分析揭示了CTC的详细遗传变异，而在单个CTC和手术标本中均检测到六个新的基因突变。这项研究为从外周血样本中分离和分析单个CTC提供了有用的工具，不仅有助于癌症的早期诊断，而且有助于在单细胞水平上揭示肿瘤的遗传信息。©2019国际细胞计数学会。这不仅有助于癌症的早期诊断，而且有助于在单细胞水平上揭示肿瘤的遗传信息。©2019国际细胞计数学会。这不仅有助于癌症的早期诊断，而且有助于在单细胞水平上揭示肿瘤的遗传信息。©2019国际细胞计数学会。

更新日期：2020-01-10

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