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Efficient isolation and quantification of circulating tumor cells in non-small cell lung cancer patients using peptide-functionalized magnetic nanoparticles
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475553/ https://www.ncbi.nlm.nih.gov/pubmed/32944338 http://dx.doi.org/10.21037/jtd-20-1026A |
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author | Liang, Naixin Liu, Lei Li, Ping Xu, Yuan Hou, Yingshuo Peng, Jiaxi Song, Yang Bing, Zhongxing Wang, Yadong Wang, Yanyu Jia, Ziqi Yang, Xiaoying Li, Da Xu, Huihui Yu, Qian Li, Shanqing Hu, Zhiyuan Yang, Yanlian |
author_facet | Liang, Naixin Liu, Lei Li, Ping Xu, Yuan Hou, Yingshuo Peng, Jiaxi Song, Yang Bing, Zhongxing Wang, Yadong Wang, Yanyu Jia, Ziqi Yang, Xiaoying Li, Da Xu, Huihui Yu, Qian Li, Shanqing Hu, Zhiyuan Yang, Yanlian |
author_sort | Liang, Naixin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7475553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-74755532020-09-16 Efficient isolation and quantification of circulating tumor cells in non-small cell lung cancer patients using peptide-functionalized magnetic nanoparticles Liang, Naixin Liu, Lei Li, Ping Xu, Yuan Hou, Yingshuo Peng, Jiaxi Song, Yang Bing, Zhongxing Wang, Yadong Wang, Yanyu Jia, Ziqi Yang, Xiaoying Li, Da Xu, Huihui Yu, Qian Li, Shanqing Hu, Zhiyuan Yang, Yanlian J Thorac Dis Original Article 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. AME Publishing Company 2020-08 /pmc/articles/PMC7475553/ /pubmed/32944338 http://dx.doi.org/10.21037/jtd-20-1026A Text en 2020 Journal of Thoracic Disease. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Liang, Naixin Liu, Lei Li, Ping Xu, Yuan Hou, Yingshuo Peng, Jiaxi Song, Yang Bing, Zhongxing Wang, Yadong Wang, Yanyu Jia, Ziqi Yang, Xiaoying Li, Da Xu, Huihui Yu, Qian Li, Shanqing Hu, Zhiyuan Yang, Yanlian Efficient isolation and quantification of circulating tumor cells in non-small cell lung cancer patients using peptide-functionalized magnetic nanoparticles |
title | Efficient isolation and quantification of circulating tumor cells in non-small cell lung cancer patients using peptide-functionalized magnetic nanoparticles |
title_full | Efficient isolation and quantification of circulating tumor cells in non-small cell lung cancer patients using peptide-functionalized magnetic nanoparticles |
title_fullStr | Efficient isolation and quantification of circulating tumor cells in non-small cell lung cancer patients using peptide-functionalized magnetic nanoparticles |
title_full_unstemmed | Efficient isolation and quantification of circulating tumor cells in non-small cell lung cancer patients using peptide-functionalized magnetic nanoparticles |
title_short | Efficient isolation and quantification of circulating tumor cells in non-small cell lung cancer patients using peptide-functionalized magnetic nanoparticles |
title_sort | efficient isolation and quantification of circulating tumor cells in non-small cell lung cancer patients using peptide-functionalized magnetic nanoparticles |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475553/ https://www.ncbi.nlm.nih.gov/pubmed/32944338 http://dx.doi.org/10.21037/jtd-20-1026A |
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