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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell

Javier Mariscal1, Marta Alonso-Nocelo1, Laura Muinelo-Romay1,2

  • 1Translational Medical Oncology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela, Spain.

Scientific Reports
|December 1, 2016
PubMed

Insights

Molecular profiling of circulating tumor cells in Non-Small Cell Lung Cancer (NSCLC) reveals key biomarkers. These markers, including NOTCH1, can predict progression-free survival and may offer new therapeutic targets for lung cancer dissemination.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) is not fully understood.
  • Gaps exist in understanding the dynamic role of disseminating tumor cells due to challenges in molecular profiling.

Purpose of the Study:

  • To investigate the molecular mechanisms of metastasis in NSCLC by analyzing circulating tumor cells (CTCs).
  • To identify specific biomarkers for monitoring NSCLC progression and potential therapeutic targets.

Main Methods:

  • Global gene expression analysis of EpCAM-positive CTCs from advanced NSCLC patients.
  • Immunoisolation and whole genome amplification techniques were employed.
  • Validation of candidate genes using RT-qPCR on an independent patient cohort.

Main Results:

  • Identified an EpCAM+ CTC-specific expression profile linked to cellular movement, adhesion, and signaling pathways (PI3K/AKT, ERK1/2, NF-kB).
  • NOTCH1 identified as a key driver, with NOTCH1, PTP4A3, LGALS3, and ITGB3 validated as prognostic markers.
  • These markers showed significant prognostic value for Progression-Free Survival (PFS).

Conclusions:

  • Molecular characterization of EpCAM+ CTCs offers potential as a 'liquid biopsy' for NSCLC patient monitoring.
  • NOTCH1 is confirmed as a potential therapeutic target to inhibit lung cancer spread.

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