VCAN, expressed highly in hepatitis B virus-induced hepatocellular carcinoma, is a potential biomarker for immune checkpoint inhibitors

doi:10.4251/wjgo.v14.i10.1933

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World Journal of Gastrointestinal Oncology

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World J Gastrointest Oncol. Oct 15, 2022; 14(10): 1933-1948
Published online Oct 15, 2022. doi: 10.4251/wjgo.v14.i10.1933

Table 1 Correlation between VCAN expression and clinical characteristics in The Cancer Genome Atlas Liver Hepatocellular Carcinoma

Characteristic	Low VCAN	High VCAN	P value
n	187	187
Age, n (%)			0.020
60	77 (20.6)	100 (26.8)
> 60	110 (29.5)	86 (23.1)
Gender, n (%)			0.015
Female	49 (13.1)	72 (19.3)
Male	138 (36.9)	115 (30.7)
Pathologic stage, n (%)			0.042
I & II	138 (39.4)	122 (34.8)
III & IV	41 (11.7)	45 (14.0)
Histologic grade, n (%)			0.090
G1	34 (9.2)	21 (5.7)
G2	88 (23.8)	90 (24.4)
G3	54 (14.6)	70 (19)
G4	8 (2.2)	4 (1.1)
AFP (ng/mL), median (IQR)	9 (3.5, 140)	23 (5, 419)	0.039

AFP: Alpha-fetoprotein; IQR: Interquartile range.

Table 2 Clinical features and VCAN expression in patients with hepatocellular carcinoma and liver cirrhosis caused by hepatitis B virus

Clinical feature	HCC (n = 50)	Liver cirrhosis (n = 50)	P value
Age	57.55 ± 1.80	54.05 ± 2.22	0.227
Sex (male/female)	8/32	30/10	0.705
Anti-virus treatment (yes/no)	26/14	20/20	0.337
HBeAg (+/-)	7/33	6/34	0.144
HBV-DNA (IU/mL): ≤ 10²/> 10²	22/18	11/29	0.100
Child-Pugh: A/B&C	28/17	8/32	0.168
VCAN mRNA (%)	4.45 ± 0.56	3.83 ± 0.61	0.147
VCAN methylation	0.056 ± 0.009	0.047 ± 0.005	0.022

HCC: Hepatocellular carcinoma; HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen.

Table 3 Correlation between VCAN mRNA expression and clinical features

Variable	VCAN RNA expression (median as cutoff)		P value
Variable	Low	High	P value
Age	56.60 ± 8.45	55.00 ± 9.82	0.552
Male/female	39/11	38/12	0.705
Anti-viral treatment/no treatment	23/27	35/15	0.110
HBeAg (+)/(-)	21/29	5/45	0.028
HBV-DNA (IU/mL): ≤ 10²/> 10²	13/37	34/16	0.025
Child-Pugh: A/B&C	35/15	31/19	0.490
AFP (ng/mL)	11.59 (3.47, 135.68)	21.43 (1.84, 210.88)	0.698
Total bilirubin (μmol/L)	26.37 (18.70, 50.25)	16.26 (11.47, 29.14)	0.035
Direct bilirubin (μmol/L)	8.44 (6.64, 27.92)	5.28 (3.51, 13.96)	0.043
Indirect bilirubin (μmol/L)	17.21 (12.23, 22.83)	10.51 (6.78, 13.39)	0.007
Total cholesterol (mmol/L)	2.90 ± 0.82	3.56 ± 0.81	0.015
LDL-C (mmol/L)	1.74 ± 0.59	2.25 ± 0.59	0.009
WBC (× 10⁹/L)	3.54 ± 1.40	6.12 ± 2.40	< 0.001
Neutrophil (%)	58.69 ± 13.24	57.31 ± 14.48	0.302
Platelet (× 10⁹/L)	76.60 ± 49.14	172.6 ± 87.01	< 0.001
Prothrombin time (s)	11.85 (10.85, 15.55)	11.15 (10.43, 11.83)	0.030
Prothrombin activity (%)	75.64 ± 21.15	89.37 ± 12.74	0.018
Fibrinogen (mg/dL)	186.00 ± 49.53	267.55 ± 111.17	0.006

LDL-C: Low density lipoprotein cholesterol; WBC: White blood cells; HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen; AFP: Alpha-fetoprotein.

Table 4 Top 20 gene enrichment sets of highly expressed VCAN

Name	Size	ES	NES	NOM P value	FDR Q value
KEGG_FC_GAMMA_R_MEDIATED_PHAGOCYTOSIS	96	-0.739	-2.154	< 0.001	5.13E-04
KEGG_PATHOGENIC_ESCHERICHIA_COLI_INFECTION	56	-0.720	-2.046	< 0.001	5.91E-04
KEGG_ECM_RECEPTOR_INTERACTION	84	-0.716	-2.162	< 0.001	8.55E-04
KEGG_AXON_GUIDANCE	129	-0.695	-2.191	< 0.001	0.0015376
KEGG_DILATED_CARDIOMYOPATHY	90	-0.680	-2.112	< 0.001	4.91E-04
KEGG_APOPTOSIS	87	-0.678	-2.042	< 0.001	6.26E-04
KEGG_CHEMOKINE_SIGNALING_PATHWAY	188	-0.678	-2.127	< 0.001	3.83E-04
KEGG_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION	116	-0.677	-2.187	< 0.001	7.69E-04
KEGG_FOCAL_ADHESION	199	-0.675	-2.148	< 0.001	4.28E-04
KEGG_HYPERTROPHIC_CARDIOMYOPATHY_HCM	83	-0.673	-2.128	< 0.001	4.30E-04
KEGG_CELL_ADHESION_MOLECULES_CAMS	131	-0.663	-2.076	< 0.001	7.01E-04
KEGG_REGULATION_OF_ACTIN_CYTOSKELETON	213	-0.659	-2.158	< 0.001	6.42E-04
KEGG_GAP_JUNCTION	90	-0.656	-2.052	< 0.001	6.23E-04
KEGG_ENDOCYTOSIS	181	-0.656	-2.084	< 0.001	8.02E-04
KEGG_MELANOGENESIS	101	-0.630	-2.129	< 0.001	4.92E-04
KEGG_VASCULAR_SMOOTH_MUSCLE_CONTRACTION	114	-0.629	-2.097	< 0.001	7.21E-04
KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION	264	-0.625	-2.119	< 0.001	3.44E-04
KEGG_PATHWAYS_IN_CANCER	325	-0.621	-2.111	< 0.001	4.50E-04
KEGG_MAPK_SIGNALING_PATHWAY	267	-0.602	-2.080	< 0.001	7.48E-04
KEGG_CALCIUM_SIGNALING_PATHWAY	177	-0.582	-2.057	< 0.001	6.60E-04

ES: Enrichment score; NES: Normalized enrichment score; NOM: Nominal; FDR: False discovery rate; KEEG: Kyoto Encyclopedia of Genes and Genomes.

Citation: Wang MQ, Li YP, Xu M, Tian Y, Wu Y, Zhang X, Shi JJ, Dang SS, Jia XL. VCAN, expressed highly in hepatitis B virus-induced hepatocellular carcinoma, is a potential biomarker for immune checkpoint inhibitors. World J Gastrointest Oncol 2022; 14(10): 1933-1948
URL: https://www.wjgnet.com/1948-5204/full/v14/i10/1933.htm
DOI: https://dx.doi.org/10.4251/wjgo.v14.i10.1933