Journal
ANNALS OF ONCOLOGY
Volume 28, Issue 7, Pages 1523-1531Publisher
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdx156
Keywords
CTC; circulating tumor cell; non-small-cell lung cancer; vimentin; EMT; biomarker
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Funding
- European Society for Medical Oncology
- Hoffman-La Roche
- International Association for the Study of Lung Cancer
- grant DUERTECC/EURONCO (Diplome Universitaire Europeen de Recherche Translationelle et Clinique en Cancerologie)
- LabEx LERMIT [ANR-10-LABX-0033-LERMIT]
- Fondation pour la Recherche Medicale [FDT20150532072]
- Fondation de France [201300038317]
- Fondation ARC pour la Recherche sur le Cancer [20131200417]
- Innovative Medicines Initiative CANCER ID [IMI-JU-11-2013, 115749]
- Institut National du Cancer [PRT-K14-032]
- Agence Nationale de la Recherche [ANR-CE17-0006-01]
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Background: We report the first study examining the clinical, numerical and biological properties of circulating tumor cells according to molecular subtypes of non-small-cell lung cancer. Patients and methods: 125 patients with treatment-naive stage IIIb-IV NSCLC were prospectively recruited for Cell Search analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim+) CTCs with clinical characteristics, tumor genotype, and survival were assessed. Results: 51/125 patients (40.8%) were total CTC+ And 26/125 (20.8%) were vim CTC+ at baseline. Multivariate analysis showed patients with >= 5 total CTCs had significantly reduced OS (HR 0.55, 95% CI 0.33-0.92, P = 0.022) but not PFS (HR 0.68, 95% CI 0.42-1.1, P = 0.118) compared to patients with <5 total CTCs. No OS difference was evident between vim+ CTC and vim-negative CTC patients overall (HR 1.24, 95% CI 0.67-2.28, P = 0.494), but after subdivision according to NSCLC driver mutation, we found an increase of vim+ CTCs in the EGFR-mutated subgroup (N = 21/94 patients; mean 1.24 vs 1.22 vim+ CTCs, P = 0.013), a reduction of total CTCs in the ALK-rearranged subgroup (N = 13/90 patients; mean 1.69 vs 5.82 total CTCs, P = 0.029), and a total absence of vim+ CTCs in KRAS-mutated adenocarcinomas (N = 19/78 patients; mean 0 vs 1.4 vim+ CTCs, P = 0.006). Conclusions: We validate that the baseline presence of >= 5 total CTCs in advanced NSCLC confers a poor prognosis. CTCs from EGFR-mutant NSCLC express epithelial-mesenchymal transition characteristics, not seen in CTCs from patients with KRAS-mutant adenocarcinoma.
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