RT Journal Article
T1 Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer
A1 Mariscal, Javier
A1 Alonso Nocelo, Marta
A1 Muinelo Romay, Laura
A1 Barbazán García, Jorge
A1 Vieito, María
A1 Abalo, Alicia
A1 Gómez Tato, Antonio
A1 Casares de Cal, María de los Ángeles
A1 García-Caballero Parada, Tomás
A1 Rodríguez, Carmela
A1 Brozos, Elena
A1 Baron, Francisco
A1 López López, Rafael
A1 Abal Posada, Miguel
K1 Lung Cancer
K1 Metastasis
K1 Circulating Tumour Cells (CTCs)
K1 Liquid biopsy
K1 Biomarkers
AB Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients. We identified an EpCAM+ CTC-specific expression profile in NSCLC patients mostly associated with cellular movement, cell adhesion and cell-to-cell signalling mediated by PI3K/AKT, ERK1/2 and NF-kB pathways. NOTCH1 emerged as a driver connecting active signalling pathways, with a reduced number of related candidate genes (NOTCH1, PTP4A3, LGALS3 and ITGB3) being further validated by RT-qPCR on an independent cohort of NSCLC patients. In addition, these markers demonstrated high prognostic value for Progression-Free Survival (PFS). In conclusion, molecular characterization of EpCAM+ CTCs from advanced NSCLC patients provided with highly specific biomarkers with potential applicability as a “liquid biopsy” for monitoring of NSCLC patients and confirmed NOTCH1 as a potential therapeutic target to block lung cancer dissemination.
PB Nature Publishing Group
YR 2016
FD 2016
LK http://hdl.handle.net/10347/22923
UL http://hdl.handle.net/10347/22923
LA eng
NO Mariscal, J., Alonso-Nocelo, M., Muinelo-Romay, L. et al. Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer. Sci Rep 6, 37820 (2016). https://doi.org/10.1038/srep37820
NO This work was funded by InveNNta (Innovation in Nanomedicine); Operational Programme for Cross-border Cooperation: Spain-Portugal (POCTEP) and European Regional Development Fund (ERDF). Javier Mariscal is recipient of a fellowship from Escola de Doutoramento Internacional Campus Vida of the University of Santiago de Compostela. Laura Muinelo-Romay is supported by ISCIII as Responsible of the Liquid Biopsy Analysis Unit
DS Minerva
RD 27 abr 2026