Exploration of the Role of M2 Macrophages in Hepatocellular Carcinoma: Insights into Disulfidptosis and Cellular Interactions - PubMed
4 hours ago
- #disulfidptosis
- #hepatocellular carcinoma
- #M2 macrophages
- Study explores M2 macrophages in hepatocellular carcinoma (HCC), focusing on disulfidptosis and immune interactions using multi-omics and single-cell RNA sequencing data.
- Identified three molecular HCC subtypes; disulfidptosis-enriched subtype (subtype 1) showed better survival and unique metabolic features like glucose/glutamine enrichment.
- High-disulfidptosis tumor cells upregulate disulfidptosis genes (e.g., SLC7A11, RAC1) but downregulate traditional energy pathways, creating a paradoxical metabolic state.
- These tumor cells recruit M2 macrophages via bidirectional communication, primarily through MIF pathway from tumor to macrophages and GALECTIN/CypA pathways from macrophages to tumor.
- Found a strong positive correlation between disulfidptosis and ferroptosis, centered on M2 macrophages and stage 2, with GPX4-RAC1 axis validated via co-expression and spatial protein co-localization.
- Conclusions suggest a disulfidptosis-associated HCC subtype with a distinct metabolic-immune niche, highlighting M2 macrophage involvement and a novel link between disulfidptosis and ferroptosis.