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Volume 25, Issue 5
  • ISSN: 1389-2029
  • E-ISSN: 1875-5488

Abstract

Background

Targeted therapies have improved the clinical outcomes of most patients with cancer. However, the heterogeneity of gastric cancer remains a major hurdle for precision treatment. Further investigations into tumor microenvironment heterogeneity are required to resolve these problems.

Methods

In this study, bioinformatic analyses, including metabolism analysis, pathway enrichment, differentiation trajectory inference, regulatory network construction, and survival analysis, were applied to gain a comprehensive understanding of tumor microenvironment biology within gastric cancer using single-cell RNA-seq and public datasets and experiments were carried out to confirm the conclusions of these analyses.

Results

We profiled heterogeneous single-cell atlases and identified eight cell populations with differential expression patterns. We identified two cancer-associated fibroblasts (CAFs) subtypes, with particular emphasis on the role of inflammatory cancer-associated fibroblasts (iCAFs) in EMT and lipid metabolic crosstalk within the tumor microenvironment. Notably, we detected two differentiation states of iCAFs that existed in different tissues with discrepant expression of genes involved in immuno-inflammation or ECM remodeling. Moreover, investigation of tumor-infiltrating myeloid cells has revealed the functional diversity of myeloid cell lineages in gastric cancer. Of which a proliferative cell lineage named C1QC+MKI67+TAMs was recognized with high immunosuppressive capacities, suggesting it has immune suppression and cell proliferation functions in the tumor niche. Finally, we explored regulatory networks based on ligand-receptor pairs and found crucial pro-tumor crosstalk between CAFs and myeloid cells in the tumor microenvironment (TME).

Conclusion

These findings provide insights for future cancer treatments and drug discovery.

© 2024 Bentham Science Publishers
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2024-10-01
2024-11-14

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/content/journals/cg/10.2174/0113892029300608240531111743
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Crosstalk Between Cancer-associated Fibroblasts and Myeloid Cells Shapes the Heterogeneous Microenvironment of Gastric Cancer
Curr. Genomics 25, 390 (2024); https://doi.org/10.2174/0113892029300608240531111743
/content/journals/cg/10.2174/0113892029300608240531111743
/content/journals/cg/10.2174/0113892029300608240531111743
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  • Article Type:     Research Article
Keyword(s): cancer-associated fibroblasts; gastric cancer; ligand-receptor pairs; myeloid cells; Single-cell sequencing; tumor microenvironment

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