Mast Cells Drive Ferroptosis in Gastric Tumors as Key Players in the Tumor Immune Microenvironment

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dc.authorid0000-0002-7442-5728
dc.authorid0000-0002-9431-2296
dc.contributor.authorSert, Fatma
dc.contributor.authorUlucan, Ozlem
dc.date.accessioned2026-04-04T18:55:57Z
dc.date.available2026-04-04T18:55:57Z
dc.date.issued2025
dc.departmentİstanbul Bilgi Üniversitesi
dc.description.abstractFerroptosis, an iron-dependent form of oxidative cell death, plays a critical role in cancer progression and immune regulation. However, the functional connections of ferroptosis with specific immune cell types remain poorly defined, limiting the future possibilities to harness ferroptosis for cancer biology, diagnosis, and treatment. To address this knowledge gap, we conducted an integrated transcriptomic analysis to investigate ferroptosis-related immune dynamics in gastric cancer (GC). We utilized GC datasets from The Cancer Genome Atlas-stomach adenocarcinoma (n = 412) and the GSE66229 (n = 300) that were clustered into three GC immune subtypes based on single-sample Gene Set Enrichment Analysis scores of 29 immune gene sets. Bulk RNA-seq analysis revealed that the immune-inflamed subtype (HIS) of tumor samples in both GC datasets exhibited the highest ferroptosis enrichment and showed a positive correlation with activated mast cells and neutrophils. Given the regulatory role of mast cells in the tumor microenvironment (TME), particularly in recruiting neutrophils, we further examined their link to ferroptosis. In a fibroblast-mast cell coculture RNA-seq data (GSE223179), fibroblasts exhibited increased ferroptosis enrichment, supporting a mast cell-mediated influence. Single-cell RNA-seq data confirmed stronger interactions between mast cells and fibroblasts in GC compared to normal tissues. Specifically, they revealed a positive correlation between mast cell activity and ferroptosis enrichment in tumor-associated fibroblasts. In conclusion, these findings suggest that mast cells may promote ferroptosis in the TME through paracrine signaling, possibly via annexin and cyclophilin A. By uncovering this novel pathophysiological axis, our study reveals a previously unrecognized role of mast cells in regulating ferroptosis within the TME. The findings call for translational and experimental medical research and have potential implications for innovation toward GC diagnostics and therapeutics.
dc.identifier.doi10.1177/15578100251366980
dc.identifier.doi10.1177/15578100251366980
dc.identifier.endpage441
dc.identifier.issn1536-2310
dc.identifier.issn1557-8100
dc.identifier.issue9
dc.identifier.pmid40831393
dc.identifier.scopus2-s2.0-105013646658
dc.identifier.scopusqualityQ2
dc.identifier.startpage429
dc.identifier.urihttps://doi.org/10.1177/15578100251366980
dc.identifier.urihttps://hdl.handle.net/11411/10635
dc.identifier.volume29
dc.identifier.wosWOS:001553892100001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMary Ann Liebert, Inc
dc.relation.ispartofOmics-A Journal of Integrative Biology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20260402
dc.snmzKA_Scopus_20260402
dc.subjectFerroptosis
dc.subjectTumor Immune Microenvironment
dc.subjectMast Cells
dc.subjectGastric Cancer
dc.subjectScrna-Seq
dc.subjectIntegrative Biology
dc.titleMast Cells Drive Ferroptosis in Gastric Tumors as Key Players in the Tumor Immune Microenvironment
dc.typeArticle

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