Genetic and epigenetic aspects of initiation and progression of hepatocellular carcinoma

Table 3 Genes epigenetically suppressed in hepatocellular carcinoma through promoter hypermethylation

Symbol (location)	Biological function	Expression	n	Relevant clinical factors	Functional analyses	Interacting molecules	In vivo	Ref.
CLDN3 (7q11.23)	Integral membrane protein and a component of tight junction strands	mRNA, IHC	114	OS	Motility, invasion, tumor formation	Wnt, EMT, β-catenin	Yes	99
DENND2D (1p13.3)	Membrane trafficking protein regulating Rab GTPases	mRNA, IHC	92	OS, RFS	-	-	-	100
DPT (1q12-q23)	Cell-matrix interactions and matrix assembly	mRNA, IHC, WB	202	OS, RFS, AFP, vascular invasion, differentiation	Migration, metastasis	RhoA, FAK, c-SRC, α3β1 integrin	Yes	98
DPYSL3 (5q32)	Cell-adhesion factor involved in the metastatic process of tumor cells	mRNA, IHC	151	OS, RFS, AFP, PIVKAII, gender, vascular invasion, serosal invasion	Migration, invasion	VEGF, FAK	-	105
EFEMP1 (2p16)	Extracellular matrix glycoproteins	mRNA	48	OS, liver damage, AFP	-	-	-	103
FBLN1 (22q13)	Secreted fibrillar extracellular matrix protein	mRNA, IHC, WB	48	number, size, stage	-	-	-	96
MEG3 (14q32)	Unknown	mRNA	72	OS, RFS, tumor size and Edmondson grade	Proliferation, apoptosis	p53, UHRF1	Yes	102
MT1G (16q13)	Preserve the homeostasis of metals	mRNA	48	none	-	-	-	11
PDSS2 (6q16.3-21)	Synthesis of coenzyme Q10	mRNA, IHC	151	OS, RFS, AFP, vascular invasion, differentiation, serosal invasion, stage	-	HNF4a, CDX2	-	101
RELN (7q22)	Secreted extracellular matrix protein	mRNA	48	RFS	-	-	-	104
TIF1γ (7p22.1)	Unknown	IHC, WB	204	OS, RFS, stage	Invasion, metastasis	TGF-β/Smad	-	97
TUSC1 (9p21.2)	Unknown	mRNA, IHC	94	OS, stage	-	-	-	106

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