Genetic and epigenetic aspects of initiation and progression of hepatocellular carcinoma

Table 2 Genes suppressed in hepatocellular carcinoma; putative tumor suppressors

Symbol (location)	Biological function	Expression	n	Relevant clinical factors	Functional analyses	Interacting molecules	In vivo	Ref.
ARNT2 (15q24)	Partner for several sensor proteins of the bHLH-PAS family	IHC	195	OS, RFS, age, size, number, vascular invasion, AFP, differentiation, stage	Proliferation, invasion, migration	-	Yes	79
BTG1 (12q22)	Regulates cell growth and differentiation	mRNA, IHC	151	OS, RFS, PIVKA-II, size, differentiation, vascular invasion, stage, extra-hepatic recurrence	-	-	-	80
CDH3 (16q22.1)	Calcium-dependent cell-cell adhesion glycoprotein	IHC	69	Stage	Proliferation	-	-	71
EBP1 (12q13.2)	RNA-binding protein involved in cell growth regulation	IHC, WB	103	OS, grade, size	Growth, cell cycle	-	-	74
FBLN5 (14q32.1)	Secreted extracellular matrix protein	mRNA, IHC	86	OS, number, vascular invasion, grade, stage	Migration, invasion	MMP7	-	76
Fbxw7 (4q31.3)	Ubiquitin-mediated degradation of cyclin E	IHC	60	OS, size, vascular invasion, grade, stage	Growth, apoptosis	YAP	Yes	77
GPx3 (5q23)	Detoxification of hydrogen peroxide	mRNA, IHC, ELISA	113	OS, RFS, size, number, vascular invasion, stage	Proliferation, invasion	Erk, NFκB, SIP1	Yes	75
IGFBP-1 (7p12.3)	Mediator of the IGFs	IHC	90	OS, differentiation, cirrhosis, vascular invasion, stage	Invasion	MMP9	-	73
LGALS4 (19q13.2)	Modulating cell-cell and cell-matrix interactions	mRNA, IHC, ELISA	201	Size, differentiation, vascular invasion, stage	Migration, invasion	-	-	72
TIPE1 (19p13.3)	Unknown	IHC	50	OS, grade	Growth, apoptosis	Nec-1, Rac-1	Yes	78

IHC: Immunohistochemistry; WB: Western blotting; OS: Overall survival; RFS: Recurrence free survival; AFP: Alpha-fetoprotein; PIVKA: Protein induced by vitamin K antagonists.