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

作者：Haina Qu, Jing Zhao, Xia Zuo, Hang He, Xiaohan Wang, Huiyan Li, Kun Zhang · 发表于：PeerJ · 年份：2025 · DOI：10.7717/peerj.19072 · 被引用次数：12 · 研究领域：TGF-β signaling in diseases、Ferroptosis and cancer prognosis、Endometrial and Cervical Cancer Treatments

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 rol...