To further explore the biological functional differences between these two pairs, we conducted GO analysis and discovered that genes highly expressed in RSPO1+ fibroblasts are related to the endoplasmic reticulum, translation initiation, and membrane protein and that pathways apparently enriched in POSTN+ fibroblasts are related to extracellular matrix (ECM) organization, and antigen processing and presentation, suggesting that POSTN+ fibroblasts shape a more aggressive phenotype of HNSCC through ECM remodeling and immune regulation (Fig. 3I). Here, RSPO1 is linked to head and neck squamous cell carcinoma.