期刊
NATURE MEDICINE
卷 25, 期 10, 页码 1534-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-019-0593-1
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资金
- Cancer Research UK [C11496/A17786, C5759/A27412, C5759/A25254, FC001169, FC001202]
- CRUK Lung Cancer Centre of Excellence
- CANCER-ID Consortium [115749-Cancer-ID]
- Menarini Biomarkers Singapore PTE Ltd.
- Manchester Experimental Cancer Medicine Centre
- Manchester NIHR Biomedical Research Centre
- Manchester MRC Single Cell Research Centre [MR/M008908/1]
- Francis Crick Institute
- UK Medical Research Council [FC001169, FC001202]
- Wellcome Trust [FC001169, FC001202]
- Cancer Research UK
- CRUK Lung Cancer Centre of Excellence, Stand Up 2 Cancer (SU2C)
- Rosetrees Trust
- Butterfield and Stoneygate Trusts
- NovoNordisk Foundation [ID16584]
- Prostate Cancer Foundation
- Breast Cancer Research Foundation (BCRF)
- European Research Council (ERC) [FP7-THESEUS-617844]
- European Commission ITN [607722]
- European Research Council [835297]
- National Institute for Health Research
- University College London Hospitals Biomedical Research Centre
- Cancer Research UK University College London Experimental Cancer Medicine Centre
- The Francis Crick Institute [10233] Funding Source: researchfish
- European Research Council (ERC) [835297] Funding Source: European Research Council (ERC)
Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years(1,2). Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study(3), were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC.
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