Mariscal, JavierAlonso Nocelo, MartaMuinelo Romay, LauraBarbazán García, JorgeVieito, MaríaAbalo, AliciaGómez Tato, AntonioCasares de Cal, María de los ÁngelesGarcía-Caballero Parada, TomásRodríguez, CarmelaBrozos, ElenaBaron, FranciscoLópez López, RafaelAbal Posada, Miguel2020-06-092020-06-092016Mariscal, 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/srep37820http://hdl.handle.net/10347/22923Knowledge 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.eng© The Author(s) 2016. Open Access. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/Lung CancerMetastasisCirculating Tumour Cells (CTCs)Liquid biopsyBiomarkersjournal article10.1038/srep378202045-2322open access