Matrix stiffness-related extracellular matrix signatures and the DYNLL1 protein promote hepatocellular carcinoma progression through the Wnt/β-catenin pathway

作者：Yang Shen, Jiayu Chen, Zhuolin Zhou, Jingyu Wu, Xinyao Hu, Yangtao Xu, Jiayi Li, Ling Wang, Siyu Wang, Shu‐Hong Yu, Ling Feng, Ximing Xu · 发表于：BMC Cancer · 年份：2024 · DOI：10.1186/s12885-024-12973-5 · 被引用次数：4 · 研究领域：Wnt/β-catenin signaling in development and cancer、Ferroptosis and cancer prognosis、Hepatocellular Carcinoma Treatment and Prognosis

BACKGROUND: In hepatocellular carcinoma (HCC) treatment, first-line targeted therapy in combination with immune checkpoint inhibitors (ICIs) has improved patient prognosis, but the 5-year survival rate is far from satisfactory. Studies have shown that the extracellular matrix (ECM) is an essential part of the tumour microenvironment (TME) and participates in the progression of malignant tumours. ECM remodelling can enhance matrix stiffness in cirrhosis patients, induce an immunosuppressive microenvironment network, and affect the efficacy of targeted therapies and ICIs for treating HCC. However, the exact mechanism is still unclear. METHODS: We downloaded data from public databases, selected differentially expressed ECM proteins associated with matrix stiffness, constructed and validated a prognostic model of HCC using Lasso Cox regression, and investigated the roles and mechanism of one of the ECM proteins, dynein light chain LC8-type 1 (DYNLL1), in HCC proliferation, migration, and apoptosis via in vitro experiments. RESULTS: In this study, the risk score of the matrix stiffness-related ECM protein model effectively predicted the prognosis of HCC patients. The high- and low-risk subgroups of the model also showed differences in immune cells, immune functions, and drug sensitivity. DYNLL1 promoted HCC cell progression and migration and inhibited HCC cell apoptosis through the Wnt/β-catenin pathway in vitro. CONCLUSION: The expression of matrix stiffness-related ECM proteins ...