Single-cell and bulk transcriptome analysis unveils a ligand-receptor-based signature for prognostication and reveals that TREM1 controls the malignant behaviors of hepatocellular carcinoma

• A novel ligand-receptor-based prognostic signature for HCC was developed using single-cell and bulk transcriptome data, validated across multiple cohorts. • TREM1 promotes HCC cell proliferation, migration, and inhibits apoptosis, and modulates proinflammatory cytokines (IL-1β, TNF-α, MCP-1). • TREM1 knockdown alters tumor immune microenvironment by changing M1 macrophage and Treg proportions, and affects the Nrf2/Keap1 oxidative stress pathway. • The study provides a comprehensive single-cell atlas of the HCC ecosystem, revealing immune heterogeneity between low- and high-risk patients.