Role of Cancer-Associated Fibroblasts in Prognostic Stratification of Advanced-Stage Gastric Cancer through Interacting with Endothelial and Malignant Epithelial Cells [AGC RNA-seq]

Here, we conducted patient stratification based on unsupervised clustering of transcriptomic profile of 108 normal/tumor AGC pairs and integrated single-cell RNA transcriptome profile of 116 gastric cancer/normal samples, revealing the heterogeneity of AGC, which can be stratified into distinct AGC-related signature (AGCRS)-based patient groups with different prognosis.

AGCRS scores are over-presented in cancer-associated fibroblasts (CAF) and increase in metastasis-enriched subtypes (e.g., myofibroblastic CAF). More prolific cell-cell communications were observed between CAF and metastasis-enriched epithelial/endothelial through collagen-related interactions. Experimentally, CAF conditional-medium can enhance the tube formation of endothelial cells and HOXC-AS2-related migration ability of gastric cancer cells.