Comprehensive analysis of the tumor immune microenvironment in gastric cancer and peritoneal metastasis based on single-cell RNA sequencing analysis

Background: The development and metastasis of gastric cancer is a complex process involving the TME and the interactions between various cell types. This article aims to explore the molecular mechanisms and biological processes underlying gastric cancer and its metastasis using scRNA-seq technique, with the hope of identifying new targets and approaches for clinical treatment. Methods: Utilizing R version 4.4.1 and the Seurat V5 package to process 20 scRNA-seq samples sourced from the GEO database. Highly variable genes were selected for GO, KEGG and GSAV enrichment analyses. CytoTRACE, CellChat, and Monocle3 were conducted to investigate cell communication and pseudotemporal dynamics in the PM and GC groups. Additionally, the prognostic significance of key genes was assessed by integrating data from the TCGA clinical database. Results: A total of 2,626,594 peritoneal metastasis cells and 17,894 gastric cancer cells were identified, revealing 13 distinct cell clusters. Gene enrichment analyses highlight high expression in pathways such as P53, Wnt, JAK-STAT3 in TAMs and mast cells. Cell communication was more robust in GC group than PM group, with TAMs and mast cells showing elevated expression of the CCL5-CCR1 ligand-receptor signaling axis in both groups. Pseudotemporal analysis demonstrated the differentiation potential of TAMs into mast cells, with APOC1, C1QB, FCN1, FTL, S100A9, CD1C, CD1E, and FCER1A identified as the top 8 genes driving this process. High expression of these genes, along with CCL5 and CCR1, was associated with poor long-term survival in cancer patients. Conclusion: scRNA-seq helps to unveil the intricate tumor immune microenvironment, highlighting the pivotal roles of TAMs and mast cells in gastric cancer peritoneal metastasis. The CCL5-CCR1 pathway emerges as a potential immune checkpoint, offering novel insights for future immunotherapeutic and targeted therapeutic strategies in the treatment of gastric cancer peritoneal metastasis.