Lactate metabolism-driven tumor heterogeneity and molecular signatures in intrahepatic cholangiocarcinoma

Figure 4 Biological function analysis of lactate metabolism activity subgroups in intrahepatic cholangiocarcinoma. A: Number and strength of intercellular interactions in intrahepatic cholangiocarcinoma (ICC) tumor microenvironment; B: Outgoing and incoming signaling patterns in ICC microenvironment; C: Scatter plot comparing outgoing vs incoming interaction strength of cell types; D: Ligand-receptor interaction analysis for malignant lactate metabolism (LM) cells; E and F: Interaction pairs of cell types interacting with malignant LM activity cells in providing ligand and receptor; G: PROGENy pathway activity heatmap showing elevated oncogenic signaling in LM activity subgroups; H: GSVA enrichment of hallmark pathways distinguishing high-LM and low-LM; I: Metabolic pathway enrichment analysis in LM activity subgroups. NK: Natural killer; DC: Dendritic cell; LLM: Low-lactate metabolism; ILM: Intermediate-lactate metabolism; HLM: High-lactate metabolism; PI3K: Phosphatidylinositol 3-kinase; TGF: Transforming growth factor; VEGF: Vascular endothelial growth factor; NF-κB: Nuclear factor kappa-B; TNF: Tumor necrosis factor; JAK-STAT: Janus kinase-signal transducer and activator of transcription; MAPK: Mitogen-activated protein kinase; EGFR: Epidermal growth factor receptor.