Transcriptomic features of FAP+ cells across molecular subtypes of breast cancer

Understanding subtype-specific variability of functional programs in FAP+ tumor-associated fibroblasts (TAFs) is fundamental for developing effective therapeutic strategies targeting stromal components. The aim of this study was to identify subtype-specific signaling pathways, markers, and molecular features of FAP+ TAFs. Using spatial transcriptomic analysis, we demonstrated that FAP+ TAFs in luminal breast cancer exhibit a phenotype characterized by extracellular matrix organization (GO:0030198, FDR q-value = 0.0307) and expression of genes associated with metastasis (COL10A1, MMP13, CXCL14, TSPAN8). In contrast, FAP+ TAFs in triple-negative breast cancer display a pronounced immunomodulatory phenotype with overexpression of immunosuppressive genes (CD36, PLA2G2A, CHI3L1) and enrichment of immune response-related pathways (immune response (GO:0006955, FDR q-value = 7.85e-17), inflammatory response (GO:0006954, FDR q-value = 2.79e-11), regulation of cytokine production (GO:0001817, FDR q-value = 3.39e-10)). We also identified subtype-specific gene signatures related to radioresistance: luminal A and B subtypes showed activation of DNA repair pathways (IGF1R, ERBB3, CRIP1), while triple-negative tumors demonstrated enrichment of epithelial-mesenchymal transition and stemness markers (ZEB2, NOTCH4, FOXM1). These findings emphasize that FAP+ fibroblasts are not a homogeneous population but functionally specialize depending on tumor subtype — acting as stromal architects in luminal breast cancer and as regulators of immune response in triple-negative breast cancer.