TGF-β-mediated activation of fibroblasts in cervical cancer: implications for tumor microenvironment and prognosis.

Background: Cervical cancer (CC) is a prevalent female malignancy strongly influenced by the tumor microenvironment (TME). This study focuses on the role of TGF-β signaling in cancer-associated fibroblasts (CAFs) and its interaction with immune cells, aiming to elucidate its impact on CC progression. Methods: The TME of CC patients was analyzed using scRNA-seq data and we identified the major cell types in the TME with a focus on the activation of the TGF-β signaling pathway in fibroblasts. Gene modules related to the TGF-β signaling pathway were identified by Weighted correlation network analysis (WGCNA). Using The Cancer Genome Atlas Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC) dataset, a prognostic gene model was constructed by univariate Cox, LASSO Cox and multivariate Cox regression analyses. For cellular validation, the mRNA level of prognostic model-related genes was tested via quantitative real-time real-time polymerase chain reaction (PCR). Thereafter, the following assays, including cell counting kit-8, scratch and wound healing assays, were applied to assess the viability, migration and invasion of CC cells. Results: Analysis at single-cell resolution identified nine major cell types in the TME, and significant activation of the TGF-β signaling pathway in fibroblasts was correlated with tumor proliferation and differentiation. Strong TGF-β signaling communication between fibroblasts and macrophages and NK/T cells suggested a crucial role in the shaping of the immunosuppressive microenvironment. WGCNA analysis identified gene modules significantly associated with the TGF-β signaling pathway. The prognostic model constructed based on three genes, Conclusion: This study confirmed the important role of the TGF-β signaling pathway in CC, especially in fibroblasts on tumor microenvironment and tumor progression. The current model could effectively evaluate the prognosis of CC, providing a theoretical foundation for developing CC therapies according to the TGF-β signaling pathway. The present results provide new perspectives for further research on the pathological mechanisms and clinical management of CC.