NSCLC Extracellular Vesicles Containing miR-374a-5p Promote Leptomeningeal Metastasis by Influencing Blood‒Brain...

Area of Science:

• Oncology
• Molecular Biology
• Biomarker Discovery

Background:

• Leptomeningeal metastasis (LM) is a severe complication of non-small cell lung cancer (NSCLC).
• Diagnosing and monitoring NSCLC-LM presents significant clinical challenges.
• Extracellular vesicle (EV) microRNAs (miRNAs) are emerging as promising noninvasive biomarkers.

Purpose of the Study:

• To investigate the clinical utility and role of EV miRNAs in NSCLC-LM.
• To identify diagnostic biomarkers for LM in NSCLC patients using EV miRNA profiling.
• To explore the pathogenic mechanisms by which EV miRNAs contribute to NSCLC-LM.

Main Methods:

• Next-generation sequencing of serum EV miRNAs from NSCLC patients with and without LM.
• In vitro and in vivo experiments to elucidate the role of EV miRNAs in LM pathogenesis.
• Analysis of serum EV miR-374a-5p levels and correlation with patient survival.

Main Results:

• Differential expression of EV miRNAs was detected between NSCLC patients with and without LM.
• Serum levels of EV-associated miR-374a-5p were significantly higher in patients with LM and correlated with survival.
• EV miR-374a-5p was found to disrupt endothelial cell tight junctions, increasing blood-brain barrier permeability and promoting LM by targeting γ-adducin.

Conclusions:

• Serum NSCLC-derived EV miR-374a-5p plays a role in premetastatic niche formation by increasing blood-brain barrier permeability.
• EV miR-374a-5p can serve as a valuable blood biomarker for the diagnosis and prognosis of NSCLC-LM.