Abstract
Circulating tumor cells (CTCs) invade blood vessels in solid tumors and promote metastases by circulating in the blood. CTCs are thus recognized as targets for liquid biopsy and can provide useful information for design of treatments. This diagnostic approach must consider not only the number of CTCs but also their molecular and genetic characteristics. For this purpose, use of devices that enrich CTCs independent of these characteristics and detectors that recognize various CTC characteristics is essential. In the present study, we developed a CTC detection system comprising ClearCell FX and ImageStream Mark II. We clarified the analytical performance of this system by evaluating recovery rate, lower limits of detection, and linearity. These parameters are critical for detecting rare cells, such as CTCs. We tested these parameters using three cell lines with different expression levels of the epithelial marker-epithelial cell adhesion molecule (EpCAM) and spiked these cells into whole-blood samples from healthy donors. The average recovery rate and lower limit of detection were approximately 40% and five cells/7.5 mL of whole blood, respectively. High linearity was observed for all evaluated samples. We also evaluated the ability of the system to distinguish between normal and abnormal cells based on protein expression levels and gene amplification and found that the system can identify abnormal cells using these characteristics. The CTC detection system thus displays the ability to distinguish specific characteristics of CTC, thereby providing valuable information for cancer treatment.
Highlights
Circulating tumor cells (CTCs) are solid cancer-derived cells that circulate in blood [1,2,3]
Understanding the characteristics of CTCs requires detectors with high specificity and throughput. We developed such a CTC detection system by combining a CTC enrichment device that does not rely on molecular expression with a CTC detection device that yields high-throughput and high-resolution images based on flow cytometry
The CTC detection system is based on improving cancer treatments by stably recovering heterogeneous CTCs and detecting molecular and genetic characteristics with high specificity
Summary
Circulating tumor cells (CTCs) are solid cancer-derived cells that circulate in blood [1,2,3]. CTCs are essential for cancer metastasis [4,5]. The relationship between CTCs and cancer metastasis has been studied for various types of cancer, and the presence of CTCs is a substantial risk factor for cancer metastasis and reduced survival [6,7,8,9,10]. CTCs have attracted attention as targets for liquid biopsy because they display characteristics that reflect primary and metastatic lesions [11].
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