Circulating tumor cell detection and single‐cell analysis using an integrated workflow based on ChimeraX®‐i120 Platform: A prospective study

Circulating tumor cell (CTC) analysis holds great potential to be a noninvasive solution for clinical cancer management. A complete workflow that combined CTC detection and single‐cell molecular analysis is required. We developed the ChimeraX®‐i120 platform to facilitate negative enrichment, immunof...

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Main Authors: Peng‐Xiang Wang, Yun‐Fan Sun, Wei‐Xiang Jin, Jian‐Wen Cheng, Hai‐Xiang Peng, Yang Xu, Kai‐Qian Zhou, Li‐Meng Chen, Kai Huang, Sui‐Yi Wu, Bo Hu, Ze‐Fan Zhang, Wei Guo, Ya Cao, Jian Zhou, Jia Fan, Xin‐Rong Yang
Format: Article
Language:English
Published: Wiley 2021-09-01
Series:Molecular Oncology
Subjects:
Online Access:https://doi.org/10.1002/1878-0261.12876
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author Peng‐Xiang Wang
Yun‐Fan Sun
Wei‐Xiang Jin
Jian‐Wen Cheng
Hai‐Xiang Peng
Yang Xu
Kai‐Qian Zhou
Li‐Meng Chen
Kai Huang
Sui‐Yi Wu
Bo Hu
Ze‐Fan Zhang
Wei Guo
Ya Cao
Jian Zhou
Jia Fan
Xin‐Rong Yang
author_facet Peng‐Xiang Wang
Yun‐Fan Sun
Wei‐Xiang Jin
Jian‐Wen Cheng
Hai‐Xiang Peng
Yang Xu
Kai‐Qian Zhou
Li‐Meng Chen
Kai Huang
Sui‐Yi Wu
Bo Hu
Ze‐Fan Zhang
Wei Guo
Ya Cao
Jian Zhou
Jia Fan
Xin‐Rong Yang
author_sort Peng‐Xiang Wang
collection DOAJ
description Circulating tumor cell (CTC) analysis holds great potential to be a noninvasive solution for clinical cancer management. A complete workflow that combined CTC detection and single‐cell molecular analysis is required. We developed the ChimeraX®‐i120 platform to facilitate negative enrichment, immunofluorescent labeling, and machine learning‐based identification of CTCs. Analytical performances were evaluated, and a total of 477 participants were enrolled to validate the clinical feasibility of ChimeraX®‐i120 CTC detection. We analyzed copy number alteration profiles of isolated single cells. The ChimeraX®‐i120 platform had high sensitivity, accuracy, and reproducibility for CTC detection. In clinical samples, an average value of > 60% CTC‐positive rate was found for five cancer types (i.e., liver, biliary duct, breast, colorectal, and lung), while CTCs were rarely identified in blood from healthy donors. In hepatocellular carcinoma patients treated with curative resection, CTC status was significantly associated with tumor characteristics, prognosis, and treatment response (all P < 0.05). Single‐cell sequencing analysis revealed that heterogeneous genomic alteration patterns resided in different cells, patients, and cancers. Our results suggest that the use of this ChimeraX®‐i120 platform and the integrated workflow has validity as a tool for CTC detection and downstream genomic profiling in the clinical setting.
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spelling doaj.art-0404e2d999594741806a47d454e262e22022-12-21T18:49:03ZengWileyMolecular Oncology1574-78911878-02612021-09-011592345236210.1002/1878-0261.12876Circulating tumor cell detection and single‐cell analysis using an integrated workflow based on ChimeraX®‐i120 Platform: A prospective studyPeng‐Xiang Wang0Yun‐Fan Sun1Wei‐Xiang Jin2Jian‐Wen Cheng3Hai‐Xiang Peng4Yang Xu5Kai‐Qian Zhou6Li‐Meng Chen7Kai Huang8Sui‐Yi Wu9Bo Hu10Ze‐Fan Zhang11Wei Guo12Ya Cao13Jian Zhou14Jia Fan15Xin‐Rong Yang16Department of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaShanghai Epione Medlab ChinaDepartment of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaShanghai Epione Medlab ChinaDepartment of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaShanghai Epione Medlab ChinaShanghai Epione Medlab ChinaDepartment of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Laboratory Medicine Zhongshan Hospital Fudan University Shanghai ChinaKey Laboratory of Carcinogenesis and Cancer Invasion Cancer Research Institute Central South University Ministry of Education Changsha ChinaDepartment of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai ChinaCirculating tumor cell (CTC) analysis holds great potential to be a noninvasive solution for clinical cancer management. A complete workflow that combined CTC detection and single‐cell molecular analysis is required. We developed the ChimeraX®‐i120 platform to facilitate negative enrichment, immunofluorescent labeling, and machine learning‐based identification of CTCs. Analytical performances were evaluated, and a total of 477 participants were enrolled to validate the clinical feasibility of ChimeraX®‐i120 CTC detection. We analyzed copy number alteration profiles of isolated single cells. The ChimeraX®‐i120 platform had high sensitivity, accuracy, and reproducibility for CTC detection. In clinical samples, an average value of > 60% CTC‐positive rate was found for five cancer types (i.e., liver, biliary duct, breast, colorectal, and lung), while CTCs were rarely identified in blood from healthy donors. In hepatocellular carcinoma patients treated with curative resection, CTC status was significantly associated with tumor characteristics, prognosis, and treatment response (all P < 0.05). Single‐cell sequencing analysis revealed that heterogeneous genomic alteration patterns resided in different cells, patients, and cancers. Our results suggest that the use of this ChimeraX®‐i120 platform and the integrated workflow has validity as a tool for CTC detection and downstream genomic profiling in the clinical setting.https://doi.org/10.1002/1878-0261.12876circulating tumor cellenumerationintegrated platformliquid biopsymachine learning‐based image recognitionsingle‐cell sequencing
spellingShingle Peng‐Xiang Wang
Yun‐Fan Sun
Wei‐Xiang Jin
Jian‐Wen Cheng
Hai‐Xiang Peng
Yang Xu
Kai‐Qian Zhou
Li‐Meng Chen
Kai Huang
Sui‐Yi Wu
Bo Hu
Ze‐Fan Zhang
Wei Guo
Ya Cao
Jian Zhou
Jia Fan
Xin‐Rong Yang
Circulating tumor cell detection and single‐cell analysis using an integrated workflow based on ChimeraX®‐i120 Platform: A prospective study
Molecular Oncology
circulating tumor cell
enumeration
integrated platform
liquid biopsy
machine learning‐based image recognition
single‐cell sequencing
title Circulating tumor cell detection and single‐cell analysis using an integrated workflow based on ChimeraX®‐i120 Platform: A prospective study
title_full Circulating tumor cell detection and single‐cell analysis using an integrated workflow based on ChimeraX®‐i120 Platform: A prospective study
title_fullStr Circulating tumor cell detection and single‐cell analysis using an integrated workflow based on ChimeraX®‐i120 Platform: A prospective study
title_full_unstemmed Circulating tumor cell detection and single‐cell analysis using an integrated workflow based on ChimeraX®‐i120 Platform: A prospective study
title_short Circulating tumor cell detection and single‐cell analysis using an integrated workflow based on ChimeraX®‐i120 Platform: A prospective study
title_sort circulating tumor cell detection and single cell analysis using an integrated workflow based on chimerax r i120 platform a prospective study
topic circulating tumor cell
enumeration
integrated platform
liquid biopsy
machine learning‐based image recognition
single‐cell sequencing
url https://doi.org/10.1002/1878-0261.12876
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