fig2
Figure 2. Mechanisms of recurrence after HCC ablation involve multiple biological processes. Autophagy activation supports cellular homeostasis[24], promoting invasion and metastasis, while EMT enhances tumor cell plasticity, fostering invasiveness and stress resistance[8]. The hypoxic microenvironment from heat-induced damage and vascular occlusion activates HIF-1α signaling, driving metabolic reprogramming, EMT, and angiogenesis[35]. Immune suppression is intensified via upregulated MDSCs[3] and TAMs[41], which inhibit effective anti-tumor immune responses and foster tumor growth. Collectively, these mechanisms allow residual tumor cells to survive, proliferate, and metastasize. Software: Adobe Illustrator (version 27.0; Adobe Inc.). HCC: Hepatocellular carcinoma; EMT: epithelial-mesenchymal transition; EMT-TFs: epithelial-mesenchymal transition-related transcription factors; Akt: protein kinase B; Wnt: Wingless/Integrated signaling pathway; ERK: extracellular signal-regulated kinase; SQSTM1: sequestosome 1; mTOR: mechanistic target of rapamycin; PI3K: phosphatidylinositol 3-kinase; p62: sequestosome 1/p62 protein; LC3B: microtubule-associated protein 1 light chain 3 beta; HIF-1α: hypoxia-inducible factor 1 alpha; BNIP3: BCL2 interacting protein 3; SNAIL: Snail family transcriptional repressor 1; TWIST: Twist family bHLH transcription factor; SLUG: Snail family transcriptional repressor 2; β-catenin: beta-catenin; MMP-2: matrix metalloproteinase-2; MMP-9: matrix metalloproteinase-9; METTL1: methyltransferase-like 1; WDR4: WD repeat domain 4; m7G: N7-methylguanosine; TGF-β: transforming growth factor beta; VEGF: vascular endothelial growth factor; O-GlcNAcylation: O-linked β-N-acetylglucosaminylation; MDSC: myeloid-derived suppressor cell; TAM: tumor-associated macrophage; LAPosome: LC3-associated phagosome; ROS: reactive oxygen species; NOX2: NADPH oxidase 2; CCL7: C-C motif chemokine ligand 7; IL-10: interleukin-10; IL-4: interleukin-4; IL-12b: interleukin-12 subunit beta; IFNγ: interferon gamma; CTL: cytotoxic T lymphocyte; DC: dendritic cell.
