Differences of core genes in liver fibrosis and hepatocellular carcinoma: Evidence from integrated bioinformatics and immunohistochemical analysis

Table 1 Gene expression profiles of GSE14323, GSE36411 and GSE89377 have 45 differentially expressed genes, including 2 downregulated genes and 43 upregulated genes in the fibrotic liver compared to normal liver

DEGs	Genes
Upregulated	C-X-C chemokine receptor type 4 (CXCR4)	SH3 domain-containing YSC84-like protein 1 (SH3YL1)	Laminins containing the α2 (LAMA2)
	Lumican (LUM)	DNA-binding protein inhibitor ID-3 (ID3)	Microfibril-associated glycoprotein 4 (MFAP4)
	Prostaglandin-H2 D-isomerase (PTGDS)	Aldo-keto reductase family 1 member B10 (AKR1B10)	Marginal zone B- and B1-Cell-specific protein (MZB1)
	Dickkopf-related protein 3 (DKK3)	Ras-related protein Rac2 (RAC2)	Suppressor of lin-12-like protein 3 (SEL1L3)
	Dermatopontin (DPT)	Annexin A13 (ANXA13)	Defensin Beta 1 (DEFB1)
	H-2 class II histocompatibility antigen gamma chain (CD74)	CAMPATH-1 antigen (CD52)	Protein unc-93 homolog A (UNC93A)
	FXYD domain-containing ion transport regulator 2 (FXYD2)	Adipocyte enhancer-binding protein 1 (AEBP1)	Interleukin-7 receptor subunit alpha (IL7R)
	C-X-C motif chemokine 9 (CXCL9)	C-X-C motif chemokine 10 (CXCL10)	Ribonuclease pancreatic (RNASE1)
	SRY-Box transcription factor 9 (SOX9)	Gelsolin (GSN)	Carbohydrate sulfotransferase 4 (CHST4)
	Vimentin (VIM)	Galectin-3-binding protein (LGALS3BP)	Platelet-derived growth factor receptor alpha (PDGFRA)
	Lectin, galactoside-binding soluble 4 (LGALS4)	Laminin subunit gamma-3 (LAMC3)	Claudin-10 (CLDN10)
	Joining chain of multimeric IgA and IgM (JCHAIN)	Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (ENPP2)	Cholesterol 25-hydroxylase (CH25H)
	Apolipoprotein L3 (APOL3)	Decorin (DCN)	Complement component C7 (C7)
	Epithelial cell adhesion molecule (EPCAM)	Keratin type I cytoskeletal 23 (KRT23)	EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1)
	Matrix metallopeptidase 7 (MMP7)
Downregulated	Small conductance calcium-activated potassium channel protein 2 (KCNN2)	Cytochrome P450 2C19 (CYP2C19)

DEGs: Differentially expressed genes.

Table 2 Gene Ontology analysis of differentially expressed genes (top 10 according to P-value)

Gene set	Description	Count	P value
GO: 0030198	Extracellular matrix organization	11	3.38E-10
GO: 0043062	Extracellular structure organization	11	1.56E-9
GO: 0005201	Extracellular matrix structural constituent	7	7.48E-8
GO: 0062023	Collagen-containing extracellular matrix	9	1.53E-7
GO: 0031012	Extracellular matrix	10	1.78E-7
GO: 0007155	Cell adhesion	15	2.78E-7
GO: 0022610	Biological adhesion	15	3.00E-7
GO: 0006935	Chemotaxis	10	0.000001284
GO: 0042330	Taxis	10	0.000001323
GO: 0005198	Structural molecule activity	11	0.000001624

Table 3 Kyoto Encyclopedia of Genes and Genomes pathway analysis of differentially expressed genes in fibrotic liver

Gene set	Description	P value	Genes
hsa04062	Chemokine signaling pathway	0.00	CXCR4, CXCL9, CXCL10, RAC2
hsa04510	Focal adhesion	0.01	LAMA2, LAMC3, PDGFRA, RAC2
hsa04810	Regulation of actin cytoskeleton	0.01	CXCR4, GSN, PDGFRA, RAC2
hsa04670	Leukocyte transendothelial migration	0.01	CLDN10, CXCR4, RAC2
hsa05200	Pathways in cancer	0.01	CXCR4, IL7R, LAMA2, LAMC3, PDGFRA, RAC2
hsa05416	Viral myocarditis	0.02	LAMA2
hsa04060	Cytokine-cytokine receptor interaction	0.02	CXCL9, CXCL10, CXCR4, IL7R
hsa00590	Arachidonic acid metabolism	0.02	CYP2C19, PTGDS
hsa04976	Bile secretion	0.03	FXYD2, KCNN2
hsa04024	cAMP signaling pathway	0.02	FXYD2, RAC2, SOX9

Table 4 Clinical and histologic data for healthy controls, chronic hepatitis B and hepatocellular carcinoma patients

	Control (n = 5)	CHB-S0 (n = 4)	CHB-S1-2 (n = 13)	CHB-S3-4 (n = 11)	HCC (n = 12)
Sex (M/F), n	3/2	2/2	6/7	8/3	11/1
Age, yr, mean ± SD	41.8 ± 9.5	33.0 ± 10.3	38.2 ± 8.1	40.3 ± 6.1	52.8 ± 10.5
HBeAg(+), n	0	2	9	7	3
HBV DNA, logIU/mL, median with IQR	-	5.5 (2.4, 8.5)	5.0 (2.5, 7.0)	4.7 (2.0, 6.6)	0 (0, 3.0)
ALT, U/L, median with IQR	19.2 (16.8, 28.7)	56.6 (45.0, 75.8)	39.3 (17.9, 66.3)	51.3 (29.6, 70.0)	54.7 (24.1, 105.8)
AST, U/L, median with IQR	20.7 (19.4, 22.5)	36.3 (27.2, 44.6)	27.3 (20.9, 39.9)	31.8 (23.8, 49.7)	54.8 (27.9, 111.6)
TBil, μmol/L, mean ± SD	18.9 ± 14.1	14.0 ± 4.3	12.8 ± 4.9	12.9 ± 4.8	16.8 ± 14.6
ALB, g/L, mean ± SD	45.9 ± 4.8	47.8 ± 4.3	46.5 ± 3.9	44.4 ± 5.0	41.3 ± 5.3
CHE, IU/L, mean ± SD	6191.3 ± 1908.0	11514.5 ± 3416.1	8887.5 ± 1964.8	7708.5 ± 2064.4	6538.7 ± 7065.7
AFP, ng/ml, mean ± SD or median with IQR	2.5 ± 1.4	2.0 ± 0.8	4.7 ± 6.1	11.3 ± 22.1	37.9 (9.3, 388.9)

F: Female; M: Male; ALT: Alanine transaminase; AST: Aspartate transaminase; TBil: Total bilirubin; ALB: Albumin; CHE: Cholinesterase; AFP: Alpha-fetoprotein; IQR: Interquartile range; HCC: Hepatocellular carcinoma; CHB: Chronic hepatitis B.