Hepatocellular carcinoma: Therapeutic advances in signaling, epigenetic and immune targets

Table 1 Known dysregulated pathways and genes in hepatocellular carcinoma with mode of action and frequency (modified from[4,5,92])

Pathways / genes	Alteration	Frequency in HCC
AKT-mTOR-MAPK signaling
RPS6KA3	Mutation	2%%-9%
TSC1 and TSC2	Mutation or deletion	3%-8%
PTEN	Mutation or deletion	1%-3%
FGF3, FGF4 and FGF19	Amplification	4%-6%
PI3KCA	Mutation	0%-2%
Angiogenesis
VEGFA	Amplification	3%-7%
Antioxidation
NFE2L2 KEAP1	Mutation Mutation	3%-6% 2%-8%
Cell cycle control/tumor suppressors
TP53*	Mutation or deletion	12%-45%
RB1	Mutation or deletion	3%-8%
CCND1*	Amplification	5%-14%
Epigenetic and chromatin remodeling
ARID1A*	Mutation or deletion	4%-17%
ARID2*	Mutation	3%-18%
BAP1	Mutation	5%[117]
Immortalization/telomere maintenance
ERT*	Promotor mutation amplification	54%-60% 5%-6%
JAK/STAT
JAK1	Mutation	5%
Metabolic pathways
Afamin apoptogenic protein 1, mitochondrial	Mutation	Up to 10%[117]
Oncogenes
MET*	Amplification	30%-50%
MYC	Amplification	4%
TGFβ pathway
Osteopontin	Mutation	Up to 40%[118]
G2/mitotic-specific cyclin-B2 Cyclin-dependent kinase 1 lymphoid enhancer-binding factor 1
Integrin α2
Wnt pathway
Catenin β1*	Mutation	11%-37%
AXIN1*	Mutation or deletion	5%-15%

HCC: Hepatocellular carcinoma.