Suppressed Expression of CXCL14 in Hepatocellular Carcinoma Tissues and Its Reduction in the Advanced Stage of Chronic HBV Infection

Figures & data

Table 1 Demographic Characteristics of Patients with Chronic HBV Infection and HBV-Free Controls

Variables	Mild Hepatitis (n=151) Group 1	Moderate to Severe Hepatitis(n=61) Group 2	HBV-Free Controls (n=180) Group 3	P value
Gender
Male	100 (66.2)	41 (67.2)	120 (66.7)
Female	51 (33.8)	20 (32.8)	60 (33.3)	0.990
Age	30.70±7.09	31.25±7.87	29.50±6.52	0.239
BMI	21.39±2.94	21.45±3.41	21.10±3.30	0.160
Marital Status
Single	40 (26.5)	19 (31.1)	62 (34.4)
Married	108 (71.5)	42 (68.9)	117 (65.0)
Divorced	3 (2.0)	0 (0.0)	1 (0.6)	0.332
Smoking Status
Smokers	17 (11.3)	13 (21.3)	28 (15.6)
Never-smokers	134 (88.7)	48 (78.7)	152 (84.4)	0.162
Alcohol Consumption
No	20 (13.2)	14 (23.0)	39 (21.7)
Yes	131 (86.8)	47 (77.0)	141 (78.3)	0.094
Family History of Hepatitis B
No	102 (67.5)	40 (65.6)	125 (69.4)
Yes	49 (32.5)	21 (34.4)	55 (30.6)	0.839
HBV Genotype
Genotype B	123 (81.5)	49 (80.3)	–
Genotype C	28 (18.5)	12 (19.7)	–	0.280

Table 2 The Genotype Distribution of CXCL14 Polymorphisms and Its Association with Chronic HBV Progression

Genotype	Group 1	Group 2	Group 3	P value	OR (95% CI)^a
rs2237061
CC	110 (72.8)	43 (70.5)	132 (73.3)	0.129^a	1.00 (Ref)
CT	33 (21.9)	10 (16.4)	39 (21.7)	0.991^b	0.78 (0.35–1.71)
TT	8 (5.3)	8 (13.1)	9 (5.0)	0.081^c	2.56 (0.90–7.25)
C	253 (83.8)	96 (78.7)	303 (84.2)	0.214 ^a	1.00 (Ref)
T	49 (16.2)	26 (21.3)	57 (15.8)	0.891 ^b	1.40 (0.82–2.38)
				0.166 ^c
rs2237062
GG	76 (50.3)	25 (41.0)	97 (53.9)	0.006^a*	1.00 (Ref)
GC	64 (42.4)	22 (36.1)	79 (43.9)	0.087^b	1.05 (0.54–2.03)
CC	11 (7.3)	14 (23.0)	4 (2.2)	<0.001^c*	3.87 (1.56–9.61)*
G	216 (71.5)	72 (59.0)	273 (75.8)	0.012 ^a	1.00 (Ref)
C	86 (28.5)	50 (41.0)	87 (24.2)	0.209 ^b	1.74 (1.13–2.71)
				<0.001 ^c
rs2547
GG	124 (82.1)	46 (75.4)	153 (85.0)	0.004^a*	1.00 (Ref)
GA	26 (17.2)	9 (14.8)	26 (14.4)	0.773^b	0.93 (0.41–2.14)
AA	1 (0.7)	6 (9.8)	1 (0.56)	0.001^c*	16.17 (1.90–138.00)*
G	274 (90.7)	101 (82.8)	332 (92.2)	0.021 ^a	1.00 (Ref)
A	28 (9.3)	21 (17.2)	28 (7.8)	0.492^b	2.04 (1.11–3.75)
				0.003^c

Notes: ^aGroup 1 vs Group 2. ^bGroup 1 vs Group 3. ^cGroup 2 vs Group 3. *P<0.05

Table 3 Comparison on Liver Function Parameters Among Patients with Chronic HBV Infection by CXCL14 Polymorphisms

Liver Function Parameters	rs2237062 GG Genotype	GC+CC Genotype	P value	rs2547 GG Genotype	GA+AA Genotype	P value
TBIL (umol/L)	18.14±6.18	29.79±4.06	0.003*	24.61±7.02	25.33±4.84	0.901
DBIL (umol/L)	4.13±3.96	9.92±4.91	0.013*	7.42±8.68	7.38±5.26	0.991
IBIL (umol/L)	15.72±10.19	19.92±17.23	0.028*	18.13±14.85	17.95±14.27	0.947
AST (U/L)	277.57±74.91	304.66±56.24	0.530	251.27±52.12	489.78±57.56	0.004*
ALT (U/L)	146.78±32.42	174.93±26.82	0.274	127.53±30.20	329.16±20.75	0.001*
TP (g/L)	73.37±8.28	74.37±4.55	0.265	74.28±4.50	72.30±11.91	0.089
GLOB (g/L)	41.34±5.33	42.48±3.48	0.077	42.18±3.54	41.03±7.22	0.147
ALB (g/L)	32.43±4.44	31.89±3.84	0.351	32.10±4.01	32.24±4.64	0.852
TF (g/L)	226.42±31.25	231.77±32.92	0.230	228.07±32.10	235.95±32.57	0.178
CP (g/L)	24.77±3.64	23.94±4.43	0.138	24.07±3.84	25.36±5.15	0.086
HA (ug/L)	98.03±8.07	117.34±9.78	0.124	98.64±7.50	157.78±7.87	0.023*

Note: * P<0.05.

Abbreviations: TBIL, total bilirubin; DBIL, direct bilirubin; IBIL, indirect bilirubin; ALT, alanine aminotransferase; AST, aspartate transaminase; TP, total protein; GLOB, globulin; ALB, albumin; TF, transferrin; CP, ceruloplasmin; HA, Hyaluronan.

Figure 1 Comparison on liver function parameters by rs2237062 (A) and rs2547 (B) genotypes. (A) DBIL, IBIL and TBIL are significantly higher in GC+CC genotype carriers of rs2237062; (B) ALT, AST and HA are elevated in GA+AA genotype carriers of rs2547.

Table 4 One-Way ANOVA of CXCL14 Level Between Three Groups

Group	CXCL14 Level (ng/mL)	F	P value
Group 1	8.10±1.03		<0.001^a*
Group 2	5.23±1.21		<0.001^b*
Group 3	11.14±1.22	683.773	<0.001^c*

Notes: ^aGroup 1 vs Group 2. ^bGroup 1 vs Group 3. ^cGroup 2 vs Group 3. *P<0.05

Table 5 Comparison on CXCL14 Level Between Genotypes Among Patients with Chronic HBV Infection

Genotype	CXCL14 Level (ng/mL)	t	P value
rs2237062 GG genotype	7.37±1.60
GC+CC genotype	7.25±1.71	0.404	0.687
rs2547 GG genotype	7.55±1.53
GA+AA genotype	7.06±1.79	2.126	0.035*

Note: *P<0.05.

Figure 2 Comparison on serum CXCL14 level by groups (A) and rs2237062 and rs2547 genotypes (B). (A) CXCL14 protein level is higher in HBV-free controls, and it decreases in patients with moderate and severe hepatitis; (B) CXCL14 protein level is significantly lower in carriers of rs2547 GA+AA genotype.