Macrophage-linked lipid metabolic signatures for HCC prognosis identified through integrated bulk and single-cell transcriptomics

Abstract

Background Macrophage-dependent immune remodeling and altered lipid metabolism are closely related to liver cancer behavior. In hepatocellular carcinoma (HCC), the survival relevance of macrophage-associated lipid metabolism genes (MLMGs) remains insufficiently characterized. This work evaluated MLMG-related molecular features connected with HCC progression and prognosis. Methods Public HCC transcriptomic and single-cell cohorts were analyzed. Macrophage-related differential genes (MRDGs) extracted from GSE149614 were combined with TCGA-HCC differentially expressed genes1 (DEGs1) and lipid metabolism-related genes (LMRGs). Shared candidates were screened through univariate Cox analysis and machine-learning procedures to obtain prognostic MLMGs and build a risk-score model. Immune profiling, enrichment analysis, cell-cell communication inference, pseudo-time reconstruction, and RT-qPCR validation were then performed. Results FABP5 and ECHS1 constituted the final two-gene prognostic signature. Risk categories were accompanied by altered immune components, including activated B cells, and pathways such as “fatty acid omega hydroxylase activity”. The high-risk group suggested potentially stronger immune escape-related features and higher checkpoint expression. Communication analysis suggested stronger interactions between CD8+ T cells and natural killer (NK) cells, whereas pseudotime analysis showed that MLMG expression may be associated with changes in CD8+ T-cell states. RT-qPCR preliminarily validated increased FABP5 expression and decreased ECHS1 expression in patients with HCC. Conclusion FABP5 and ECHS1 were selected as prognostic MLMGs in HCC. This two-gene model may provide clues for survival assessment and subsequent mechanism-oriented research.