Integrated genomic analyses identify oncogenic pathway interplay in hepatocarcinogenesis defining specific molecular subtypes - PubMed
4 hours ago
- #molecular subtypes
- #hepatocellular carcinoma
- #genomic analysis
- Integrative multi-omics analyses of 529 hepatocellular carcinoma (HCC) samples identify nine robust molecular subtypes.
- Common subtypes include CTNNB1ex3/APC (25%), TP53 (21%), and AXIN1/IRF2 (11%); rare subtypes include TP53+CTNNB1ex3 (6%), BAP1 (6%), CCNA2/E1 (6%), and HNF1A (1%).
- Two immune-related subtypes, UHot (17%) and UInterm (8%), lack defined drivers.
- AXIN1 and TP53 mutations modulate β-catenin and p53 pathways, while BAP1 loss inactivates TP53.
- The rare TP53+CTNNB1ex3 subtype is highly aggressive, with poor outcomes and TP53 mutation preceding CTNNB1 alteration.
- The refined molecular classification provides a framework for precision medicine in HCC.