The role of the S100A8/S100A9 in gastric tumor progression.
Stomach Neoplasms
/ metabolism
Calgranulin B
/ metabolism
Humans
Calgranulin A
/ metabolism
Disease Progression
Macrophages
/ metabolism
Cell Proliferation
NF-kappa B
/ metabolism
Signal Transduction
Gene Expression Regulation, Neoplastic
Cell Line, Tumor
Toll-Like Receptor 4
/ metabolism
Cell Movement
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 10 2024
09 10 2024
Historique:
received:
27
09
2023
accepted:
27
09
2024
medline:
10
10
2024
pubmed:
10
10
2024
entrez:
9
10
2024
Statut:
epublish
Résumé
Gastric premalignant lesions can develop into cancer through multiple steps and inflammation plays a critical role. The aim of this study is to uncover the characteristics of macrophages and their gene expression in premalignant gastric lesions to identify novel biomarkers and potential targets for treatment. We used the computational algorithm CIBERSORT to estimate immune cell subsets present in gastric tissue. We applied WGCNA to identify inflammation-related modules and hub genes. Single-cell analysis was used to identify macrophage sub-clusters specific to pathology. In addition, the in-vitro experiment was performed to verify the mechanism of the key inflammatory factors in the growth of gastric cancer. WGCNA identified a module that was positively correlated with pathological changes and highly related to inflammation scores. Single-cell analysis revealed a macrophage subset, and we observed that S100A8 and S100A9 + macrophages made up a significantly higher proportion in early gastric cancer (EGC) tissues. Our functional enrichment analysis suggested that these macrophages may play a role in gastric tumorigenesis through the activation of the NFκB signaling pathway. In vitro experiments verified that S100A9 can promote the proliferation and migration of AGS cells through the TLR4-NFκB signaling pathway, and the S100A8/S100A9 inhibitor Paquinimod can inhibit their proliferation and migration. Our findings suggest that S100A8 and S100A9 + macrophages may activate the TLR4-NFκB signaling pathway to promote cell proliferation and migration leading to gastric tumor progression. Macrophages with high expression of S100A8/S100A9 are critical in the progression of gastric inflammation to cancer. Cytokine S100A9 can activate the TLR4-NFκB signaling pathway and promote the proliferation and migration of gastric adenocarcinoma cells.
Identifiants
pubmed: 39384957
doi: 10.1038/s41598-024-74695-9
pii: 10.1038/s41598-024-74695-9
doi:
Substances chimiques
Calgranulin B
0
Calgranulin A
0
S100A9 protein, human
0
S100A8 protein, human
0
NF-kappa B
0
Toll-Like Receptor 4
0
TLR4 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
23574Subventions
Organisme : Scientific and Technological Innovation Project of China Academy of Chinese Medical Science
ID : CI2021A01008
Organisme : National Traditional Chinese Medicine Inheritance and Innovation Team Project
ID : ZYYCXTD-C-202210
Informations de copyright
© 2024. The Author(s).
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