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

Figure 2 Evaluation of lactate metabolism activity in intrahepatic cholangiocarcinoma. A: Kaplan-Meier analysis of the Cancer Genome Atlas-cholangiocarcinoma cohort showing that patients with high lactate metabolism (LM) activity exhibited significantly reduced overall survival compared to the low LM group (P = 0.0043); B: Violin plots comparing LM activity across major cell types within the intrahepatic cholangiocarcinoma (ICC) microenvironment; C: Heatmap of infer copy number variation (CNV) analysis identifying six epithelial clusters based on chromosomal CNV profiles; D: Boxplots illustrating significantly higher CNV scores in malignant clusters (K1, K2, K4, K5, and K6) compared with non-malignant cluster K3 (P < 0.001); E: Comparison of LM activity between normal and malignant epithelial cells, showing markedly elevated LM activity in the malignant population (P < 0.001); F and G: LM activity quantified by five computational algorithms (AUCell, UCell, singscore, single-sample Gene Set Enrichment Analysis, and AddModuleScore), consistently indicating higher LM activity in malignant epithelial cells; H: Uniform manifold approximation and projection visualization displaying the spatial distribution of LM activity scores across the ICC microenvironment; I: Heatmap of LM score distribution highlighting cell-type-specific variation. ^cP < 0.001. ^dP < 0.0001. NS: Not significant; TCGA-CHOL: The Cancer Genome Atlas-cholangiocarcinoma; LM: Lactate metabolism; NK: Natural killer; DC: Dendritic cell; CNV: Copy number variation; ssGSEA: Single-sample Gene Set Enrichment Analysis; UMAP: Uniform manifold approximation and projection.