<p>Gastric cancer (GC) is among the most lethal human malignancies with limited treatment options. Cell-cell interactions within the tumor microenvironment (TME) can promote tumor growth, yet their therapeutic value has not been fully explored. Here, bulk RNA-seq, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST) were integrated to analyze the heterogeneity of GC microenvironment. Tumor-specific GREM1+ fibroblasts and SPP1+ macrophages were significantly enriched in GC tissues and were involved in immunosuppression, inflammation regulation, and tumor progression. We then indicated that GREM1+ fibroblasts and SPP1+ macrophages were positively correlated in 12 independent GC datasets and validated their close localization by multiplex immunohistochemistry staining and spatial transcriptomics. Patients with both high GREM1+ fibroblasts and SPP1+ macrophages exhibited significantly shorter OS and showed enrichment of tumor-associated pathways. Our results demonstrated the complex interactions between GREM1+ fibroblasts and SPP1+ macrophages, which may serve as a potential therapeutic target for future treatment of GC.</p>

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Multi-omics analyses reveal interactions between GREM1+ fibroblasts and SPP1+ macrophages in gastric cancer

  • Lupeng Qiu,
  • Xiao Zhao,
  • Sheng Yao,
  • Yang Fei,
  • Yixin Gong,
  • Zishan Zhou,
  • Shunchang Jiao,
  • Jianming Xu

摘要

Gastric cancer (GC) is among the most lethal human malignancies with limited treatment options. Cell-cell interactions within the tumor microenvironment (TME) can promote tumor growth, yet their therapeutic value has not been fully explored. Here, bulk RNA-seq, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST) were integrated to analyze the heterogeneity of GC microenvironment. Tumor-specific GREM1+ fibroblasts and SPP1+ macrophages were significantly enriched in GC tissues and were involved in immunosuppression, inflammation regulation, and tumor progression. We then indicated that GREM1+ fibroblasts and SPP1+ macrophages were positively correlated in 12 independent GC datasets and validated their close localization by multiplex immunohistochemistry staining and spatial transcriptomics. Patients with both high GREM1+ fibroblasts and SPP1+ macrophages exhibited significantly shorter OS and showed enrichment of tumor-associated pathways. Our results demonstrated the complex interactions between GREM1+ fibroblasts and SPP1+ macrophages, which may serve as a potential therapeutic target for future treatment of GC.