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Molecular insights into early malignant transition of hepatocellular carcinoma - PubMed

3 hours ago
  • #Immune Evasion
  • #Hepatocellular Carcinoma
  • #Early Malignant Transition
  • Study profiles genomic and immunological landscapes of 21 very early hepatocellular carcinomas (veHCCs) arising in 17 cancer-prone dysplastic nodules (DNs).
  • 82% of cancer-prone DNs had TERT alterations, suggesting a predisposing rather than causative role in malignant transition.
  • Accumulation of copy number alterations (CNAs), not single-nucleotide variants, strongly associates with malignant transition.
  • Cancer-prone DNs show immune inactivity, differing from the chronic inflammation paradigm for HCC.
  • 43% of veHCCs exhibit an inflamed yet immune-evasive phenotype.
  • Two evolutionary scenarios proposed: CNA-dominant progression and inflamed progression with early immune evasion, highlighting potential for early immunotherapy intervention.