期刊
MOLECULAR ONCOLOGY
卷 15, 期 9, 页码 2345-2362出版社
WILEY
DOI: 10.1002/1878-0261.12876
关键词
circulating tumor cell; enumeration; integrated platform; liquid biopsy; machine learning-based image recognition; single-cell sequencing
类别
资金
- National Key Research and Development Program [2019YFC1315801, 2016YFF0101405, 2019YFC1315800, 2019YFC1315802]
- State Key Program of National Natural Science of China [81530077, 81830102]
- National Natural Science Foundation of China [81602543, 81672839, 81572823, 81772578, 81772551, 81872355]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA12020105, XDA12020103]
- Shanghai Municipal Health Commission Collaborative Innovation Cluster Project [2019CXJQ02]
- Shanghai Rising-Star Program Funding Program from the Shanghai Science and Technology Commission [19QA1402000]
- Shanghai 'Rising Stars of Medical Talent' Youth Development Program (Outstanding Youth Medical Talents), the Projects from the Shanghai Science and Technology Commission [19441905000]
- Shanghai Municipal Key Clinical Specialty
The ChimeraX(R)-i120 platform successfully combines CTC detection with single-cell molecular analysis, demonstrating high sensitivity, accuracy, and reproducibility. High CTC-positive rates were found in five types of cancer, while CTCs were rarely detected in healthy donors. In hepatocellular carcinoma patients, CTC status was significantly associated with tumor characteristics, prognosis, and treatment response.
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(R)-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(R)-i120 CTC detection. We analyzed copy number alteration profiles of isolated single cells. The ChimeraX(R)-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(R)-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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