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When Metrics Disagree: Automatic Similarity vs. LLM-as-a-Judge for Clinical Dialogue Evaluation
Building evidence-based knowledge graphs from full-text literature for disease-specific biomedical reasoning
Correction: The multifunctional RNA helicase DDX39A drives glioblastoma progression by modulating WISP1 alternative splicing that induces an immunosuppressive macrophage polarization
Oncogene, Published online: 01 April 2026; doi:10.1038/s41388-026-03756-2
Correction: The multifunctional RNA helicase DDX39A drives glioblastoma progression by modulating WISP1 alternative splicing that induces an immunosuppressive macrophage polarizationESM1 drives cancer angiogenesis and bevacizumab resistance via trioleate synthesis
Neoplasia. 2026 May;75:101298. doi: 10.1016/j.neo.2026.101298. Epub 2026 Mar 20.
ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) exhibits high recurrence rates and limited therapeutic options. Endothelial cell-specific molecule 1 (ESM1) and angiopoietin-like 4 (ANGPTL4) are implicated in tumor progression, yet their synergistic role in HCC lipid metabolism and angiogenesis remains unexplored.
METHODS: We integrated multi-omics approaches, including RNA sequencing, metabolomics, and immunoprecipitation-mass spectrometry, in HCC cell lines and patient-derived xenograft models. Key experiments involved Co-IP, Western blotting, tube formation assays, and clinical tissue microarray analysis to validate the ESM1-ANGPTL4-FASN-trioleate axis.
RESULTS: ESM1 and ANGPTL4 formed a positive feedback loop, stabilizing fatty acid synthase (FASN) to promote trioleate synthesis. Trioleate activated the NF-ΞΊB/IL-17 pathway in HCC cells and upregulated CD99 in endothelial cells, driving angiogenesis. In vivo, ESM1/ANGPTL4 knockdown suppressed tumor growth, which was rescued by trioleate supplementation. Clinical data revealed elevated ESM1/ANGPTL4 expression in bevacizumab-resistant HCC, correlating with poor prognosis.
CONCLUSIONS: The ESM1-ANGPTL4-FASN-trioleate axis orchestrates metabolic reprogramming and endothelial activation, representing a promising therapeutic target. Future studies should explore combination therapies targeting this axis and overcoming bevacizumab resistance in HCC.
PMID:41864037 | PMC:PMC13019581 | DOI:10.1016/j.neo.2026.101298