Bioinformatics and immunohistochemistry reveal the diagnostic and mechanistic role of the cuproptosis-related genes SMOC2/THY1 in liver fibrosis
Description
Cuproptosis, a newly identified form of programmed cell death, inhibits liver fibrosis in hepatic stellate cells. However, how cuproptosis influences liver fibrosis in other cells remains to be determined. We aimed to develop a diagnostic model for cuproptosis and to further investigate its role in liver fibrosis. We obtained datasets of patients with metabolic dysfunction-associated fatty liver disease from the Gene Expression Omnibus. A diagnostic model was established using WGCNA and machine learning, and the model demonstrated a satisfied accuracy in the training and validation sets. Single-cell RNA (scRNA) comfirmed that cuproptosis is highly likely to occur in hepatocytes and likely promotes liver fibrosis through communication with macrophages and dendritic cells. Immunohistochemistry analyses revealed that THY1 localized to fibroblast membranes and SMOC2 localized to hepatocytes. Molecular docking and molecular dynamics were used to identify the most suitable therapeutic drugs and suggested that breviscapine may target THY1, which may have a therapeutic effect on liver fibrosis. These findings establish a diagnostic model based on cuproptosis-related genes for liver fibrosis, identify THY1 and SMOC2 as key diagnostic biomarkers, and propose a model in which the expression of these markers in hepatocyte are associated with fibrosis progression, potentially through immune-mediated mechanisms.