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Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer

Authors :
Universidade de Santiago de Compostela. Departamento de Ciencias Morfolóxicas
Mariscal, Javier
Alonso Nocelo, Marta
Muinelo Romay, Laura
Barbazán García, Jorge
Vieito, María
Abalo, Alicia
Gómez Tato, Antonio
Casares de Cal, María Ángeles
García-Caballero Parada, Tomás
Rodríguez, Carmela
Brozos, Elena
Baron, Francisco
López López, Rafael
Abal Posada, Miguel
Universidade de Santiago de Compostela. Departamento de Ciencias Morfolóxicas
Mariscal, Javier
Alonso Nocelo, Marta
Muinelo Romay, Laura
Barbazán García, Jorge
Vieito, María
Abalo, Alicia
Gómez Tato, Antonio
Casares de Cal, María Ángeles
García-Caballero Parada, Tomás
Rodríguez, Carmela
Brozos, Elena
Baron, Francisco
López López, Rafael
Abal Posada, Miguel
Publication Year :
2016

Abstract

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.

Details

Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1400989175
Document Type :
Electronic Resource