Evidence map›Paper›PMID 41918097›Full record

ArticleBreast cancer research : BCR2026

Single-cell landscape of intratumoral heterogeneity and GABA-mediated remodeling of the immune microenvironment in breast cancer metastases.

Lina Tang

Abstract read
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Article in Breast cancer research : BCR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

1 author.

Lina TangInstitute of Trauma and Metabolism, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450001, China. tanglina@zzu.edu.cn.

Funding

Natural Science Foundation of Henan Province 232300420423Research Fund of Zhengzhou Central Hospital SR-0048
6 · The paper itself

Abstract

backgroundBreast cancer is one of the most prevalent malignant tumors among women, with its metastasis serving as a leading cause of mortality in affected patients. Recent studies have increasingly highlighted the significant role of tumor in nervation in the development and progression of breast cancer; however, the specific underlying mechanisms remain poorly understood.

methodsThis study investigated the relationship between tumor immune microenvironment (TIME) cell subpopulations, mediated by neuro-immune mechanisms in metastatic sites of breast cancer, and both disease severity and treatment response. We employed an analysis of single-cell transcriptomics (scRNA-seq) in conjunction with bulk RNA-seq data. The single-cell dataset GSE158399 was obtained from the GEO database, while bulk RNA-seq data from breast cancer patients were retrieved from UCSC Xena. The analysis utilized tools such as Seurat, CellChat, and Monocle, along with a GABA-related gene set.

resultsOur results identified 9 major cell types in the metastatic sites of breast cancer, including T cells, B cells, myofibroblasts, epithelial cells, macrophages, endothelial cells, proliferating cells, mature dendritic cells, and mast cells. Notably, the B cell subpopulation B_C2, the CD4+ T cell subpopulation CD4+Tcm, the M2 macrophage subpopulation, and the myofibroblast subpopulation Myo_C2 were associated with the GABA gene set and appeared to play crucial roles in cell differentiation and intercellular communication. The analysis of cell communication revealed that the GABA-mediated TIME model enhanced intercellular signaling, with receptor-ligand pairs such as PTN/MDK-NCL, CXCL12-CXCR4, and APP-CD74 exhibiting significant functional patterns within the samples. Additionally, the bulk RNA-seq data analysis identified the target gene COL1A2, whose expression was significantly correlated with tumor grading and metastatic status, indicating that Stage III patients had higher expression levels than those in Stage I and II, and that the N2 and N3 metastatic groups exhibited higher expression than the N0 group.

conclusionThis study suggests that GABA may reshape the TIME through the modulation of the neuro-immune axis, offering new insights for prognostic assessments and the development of therapeutic targets in breast cancer metastasis.

Indexed as

Breast Neoplasmsgamma-Aminobutyric AcidTumor MicroenvironmentFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansNeoplasm MetastasisSingle-Cell AnalysisSingle-Cell Gene Expression AnalysisTranscriptomegamma-Aminobutyric AcidBreast cancerGABAImmune microenvironmentMetastasisSingle-cell analysisTumor innervation

Identifiers

PMID41918097
PMCPMC13162450

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LicenceCC BY-NC-ND
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.