Single-cell transcriptome analysis reveals the targeting of epithelial and fibroblast interactions in ovarian cancer

Background Ovarian clear cell carcinoma (OCCC), a therapy-refractory epithelial ovarian cancer subtype with distinct tumor microenvironment (TME) features, has unclear links between cancer-associated fibroblasts (CAFs), extracellular matrix (ECM) remodeling (especially collagen deposition) and disease progression. Methods We characterized TME via single-cell RNA sequencing of 10 fresh tumor samples (4 OCCC, 6 non-OCCC), validated functions using CAF-ovarian cancer cell co-culture systems, verified the collagen-EMT axis in syngeneic mouse models with targeted inhibitors, and assessed clinical relevance via tissue microarray immunohistochemistry and survival correlation analysis. Results Single-cell data revealed enriched activated CAFs and abundant COL1A1 in OCCC. Collagen-rich ECM induced epithelial-mesenchymal transition (EMT), boosting cancer cell proliferation, invasion and metastasis; EMT pathway inhibition attenuated collagen-driven tumor growth in vivo. High COL1A1 and EMT marker (FAK, N-cadherin) expression correlated with poor prognosis. Conclusion CAF-driven collagen deposition promotes OCCC aggressiveness via EMT activation, and targeting the collagen-EMT axis may serve as a novel therapeutic strategy for this chemoresistant subtype.