ISG20 and neoplasm: TS_FR‒ showed upregulated immune-regulatory and ECM degradation proteins (IL-18, LGALS9, ISG20, and CTSB), along with enriched pathways related to actin cytoskeleton organization, RAC-GTPases, and leukocyte activation, in parallel with FR‒ tumor profiles (Fig. 2e, f), indicating that dysregulated fibroblasts and immune cells may collaborate within the dense stroma in FR‒ tumors.