• • PDGFC expression is significantly higher in CAFs than in nontumor fibroblasts (NFs), and elevated PDGFC correlates with poor prognosis in LUAD patients (p < 0.05). This establishes PDGFC as a prognostic biomarker and a candidate for targeted intervention in stroma-rich tumors.
• • CAF-derived PDGFC promotes EMT and MMP2 expression in cancer cells via the PDGFRA-MAPK/ERK pathway. MMP2, a PDGFRA-related gene, is associated with poor prognosis, indicating that PDGFC inhibition could reduce extracellular matrix degradation and metastatic dissemination.
• • PDGFC induces increased PDGFRA expression in both tumor cells and fibroblasts, creating a reciprocally positive feedback loop that accelerates fibrotic TME remodeling and malignant progression. This self-amplifying circuit represents a therapeutic vulnerability; interrupting PDGFC-PDGFRA signaling may dismantle the fibrotic barrier and enhance drug penetration.
• • PDGFC facilitates immunosuppression by promoting infiltration and polarization of Treg cells, M2 macrophages, and N2 neutrophils, while restraining NK cell infiltration. Immunoinhibitors TGFB1, CSF1R, PD-L1, PD-L2, KDR, IL10RB, and HAVCR2 may synergize with PDGFC, suggesting combination strategies to overcome immunotherapy resistance in LUAD.