Abstract
BackgroundCirculating tumor cells (CTC) shows great prospect to realize precision medicine in cancer patients.MethodsWe developed the NanoVelcro Chip integrating three functional mechanisms. NanoVelcro CTC capture efficiency was tested in stage III or IV lung adenocarcinoma. Further, ALK-rearrangement status was examined through fluorescent in situ hybridization in CTCs enriched by NanoVelcro.ResultsNanoVelcro system showed higher CTC-capture efficiency than CellSearch in stage III or IV lung adenocarcinoma. CTC counts obtained by both methods were positively correlated (r = 0.45, p < 0.05). Further, Correlation between CTC counts and pTNM stage determined by NanoVelcro was more significant than that determined by CellSearch (p < 0.001 VS p = 0.029). All ALK-positive patients had 3 or more ALK-rearranged CTC per ml of blood. Less than 3 ALK-rearranged CTC was detected in ALK-negative patients. NanoVelcro can detect the ALK–rearranged status with consistent sensitivity and specificity compared to biopsy test. Furthermore, the ALK-rearranged CTC ratio correlated to the pTNM stage in ALK-positive patients. Following up showed that CTCs counting by NanoVelcro was more stable and reliable in evaluating the efficacy of Clozotinib both in the short and long run compared with CellSearch. Changing of NanoVlecro CTC counts could accurately reflect disease progression.ConclusionNanoVelcro provides a sensitive method for CTC counts and characterization in advanced NSCLC. ALK-rearrangement can be detected in CTCs collected from advanced NSCLC patients by NanoVelcro, facilitating diagnostic test and prognosis analysis, most importantly offering one noninvasive method for real-time monitoring of treatment reaction.
Highlights
Circulating tumor cells (CTC) shows great prospect to realize precision medicine in cancer patients
CTC were detected in all advanced NSCLC ALKpositive and anaplastic lymphoma kinase (ALK)-negative patients using NanoVelcro, in 19 of 21 (90.49%) advanced NSCLC ALKpositive patients and 18 of 20 (90%) negative patients by CellSearch (Tables 1, 2)
Further analysis showed that Correlation between CTC counts and pTNM stage determined by NanoVelcro was more significant than that determined by CellSearch (p < 0.001 vs p = 0.029, Fig. 3d)
Summary
Circulating tumor cells (CTC) shows great prospect to realize precision medicine in cancer patients. CellSearch system as the most classic CTC enrichment system based on detection of tumor cells that express epithelial cell adhesion molecule (EpCAM), was effective to predict prognosis of many cancers, especially breast and lung cancers [1,2,3]. A diverse suite of techniques including biophysical (e.g., density gradient centrifugation devices, size-based filtration systems, cell dielectric properties-based isolation assays, microfluidics-based technologies, etc.) and biochemical (e.g., capture-agentlabeled immunomagnetic beads, CTCs-chip and nanoparticle enrichment devices, etc.) methodology-based enrichment assays by their different properties had been demonstrated [5, 6] One such most widely-used CTC assay CellSearch mentioned above is based on the technique of capture-agent-coated magnetic beads. The overall enrichment efficacy is still discontented by use of these techniques
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