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
Abstract
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.