期刊
JOURNAL OF THORACIC DISEASE
卷 12, 期 8, 页码 4262-4273出版社
AME PUBLISHING COMPANY
DOI: 10.21037/jtd-20-1026A
关键词
circulating tumor cell (CTC); peptide (Pep); non-small cell lung cancer (NSCLC); nanoparticle; liquid biopsy
资金
- Beijing Municipal Science and Technology Commission [Z171100002017013]
- Special Data Service for Oncology, The National Population and Health Scientific Data Sharing Platform [NCMI-ABD02-201809, NCMI-YF02N-201906]
- Ministry of Science and Technology of the People's Republic of China (MOST)
- Beijing Natural Science Foundation [7182132]
- Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences [2019-12M-1-001]
- National Key Research and Development Program of China [2017YFA0205001]
- Natural Science Foundation of China [21773042]
Background: Circulating tumor cells (CTCs) carry a wealth of information on primary and metastatic tumors critical for enhancing the understanding of the occurrence, progression and metastasis of non-small cell lung cancer (NSCLC). However, the low sensitivity of traditional tumor detection methods limits the application of CTCs in the treatment and disease surveillance of NSCLC. Therefore, CTCs isolation and detection with high sensitivity is highly desired especially for NSCLC patients, which is significant because of high occurrence and mortality. While it is very challenging because of the lower expression of CTC positive biomarkers such as epithelial cell adhesion molecules and cytokeratins (EpCAM and CKs), herein we report a method based on peptide-functionalized magnetic nanoparticles with high CTC capture efficiency, which demonstrates superiority in NSCLC clinical applications. Methods: For analysis and comparison of the peptide-functionalized magnetic nanoparticles (TumorFisher, Nanopep Corp.) and the antibody-modified magnetic beads (CellSearch, Janssen Diagnostics, LLC), two NSCLC cell lines, A549 and NCI-H1975 were chosen to measure the binding affinity and capture efficiency. In order to compare the effect of the clinical application of these two detection systems, 7 early stage patients with NSCLC were enrolled in this study. To further explore the clinical utility of CTC counting in different stages, 81 NSCLC patients in stage I-IV were enrolled for CTC enumeration and statistical analysis. Results: The binding affinities of the recognition peptide to A549 and NCI-H1975 are 76.7%+/- 11.0% and 70.1%+/- 4.8%, respectively, which is similar with the positive control group (anti-EpCAM antibodies). CTCs were captured in 5/7 (71.4%) of early stage NSCLC patients with NSCLC in TumorFisher system, which is higher than CellSearch, and the false negative of TumorFisher is much lower than CellSearch. In a larger clinical cohort, the CTC numbers of NSCLC patients varied in different stages and the overall detection rate of TumorFisher was 59/81 (72.8%), with the similar proportion in stage I (21/29, 72.4%), II (17/22, 77.3%) and III (16/21, 76.2%). Conclusions: Highly efficient CTC isolation technique based on peptide-magnetic nanoparticles was firstly applied in NSCLC patients. Compared with the antibody-based the technique, the higher CTC detection rates (71.4%) in NSCLC patient blood samples were demonstrated for the patients in different stages, I-IV, especially in early stages. This indicates the feasibility of the clinical utility of this new technique in early stage screening, prognosis and therapy evaluation of NSCLC.
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