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Neuroactive ligand-receptor interaction in gastric cancer: a comprehensive spatial single-cell analysis.

Lirong Chen¹, Xiao Li¹, Shaocong Mo¹

¹Department of Digestive Diseases, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico

|November 14, 2025

Summary

Neuroactive ligand-receptor interactions in gastric cancer are linked to poorer patient outcomes. Monocyte-macrophages expressing CHRNE promote tumor angiogenesis, suggesting CHRNE as a therapeutic target for gastric cancer.

Keywords:

CHRNE Gastric cancer Mono–Macs Neuroactive ligand–receptor interaction

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Area of Science:

Oncology
Molecular Biology
Immunology

Background:

Neuroactive ligand-receptor interactions are implicated in gastric cancer development.
The precise mechanisms remain unclear.

Purpose of the Study:

To elucidate the role of neuroactive ligand-receptor interactions in gastric cancer.
To identify key genes and cellular players involved in these interactions.
To explore their prognostic significance and therapeutic potential.

Main Methods:

Analysis of single-cell, spatial, and bulk transcriptome data.
Immunofluorescence validation in gastric cancer tissues.
Prognostic modeling and pathway activity assessment.

Main Results:

Neuroactive ligand-receptor interactions are associated with monocyte-macrophages (Mono-Macs).
High pathway activity correlates with poor prognosis, increased stromal scores, and immune checkpoint levels.
CHRNE expression in Mono-Macs (CHRNE+ Mono-Macs) promotes tumor angiogenesis via VEGFA, linking it to poor prognosis.

Conclusions:

Monocyte-macrophages are significantly influenced by neuroactive ligand-receptor interactions in gastric cancer.
CHRNE+ Mono-Macs may drive tumor progression by promoting angiogenesis.
Neuroactive ligand-receptor interactions, especially CHRNE, represent potential therapeutic targets for gastric cancer.