Abstract
Hepatocellular carcinoma (HCC) progression is closely linked to the role of macrophages. This study utilized single-cell RNA sequencing and genomic analysis to explore the characteristic genes of macrophages in HCC and their impact on patient prognosis. We obtained single-cell se-quencing data from seven HCC samples in the GEO database. Through principal component analysis and t-SNE dimensionality reduction, we identified 2,000 highly variable genes and per-formed clustering and annotation of 17 cell clusters, revealing 482 macrophage-related feature genes. A LASSO regression model based on these genes was developed to predict the prognosis of HCC patients, with validation in the TCGA-LIHC cohort demonstrating model accuracy (AUC = 0.78, 0.72, 0.71 for 1-, 3-, and 5-year survival rates, respectively). Additionally, patients in the high-risk group exhibited elevated tumor stemness scores, although no significant differences were observed in microsatellite instability (MSI) and tumor mutational burden (TMB) scores. Immune-related analyses revealed that FCER1G expression was downregulated in HCC and was associated with key pathways such as apoptosis and ferroptosis. Reduced FCER1G expression significantly affected HCC cell proliferation and migration. Our prognostic model provides new insights into precision and immunotherapy for HCC and holds significant implications for future clinical applications.