High level of intercellular adhesion molecule-1 affects prognosis of patients with hepatocellular carcinoma

Table 1 Clinical and biochemical data of examined patients

Parameter	mean ± SD
Age (yr)	49.38 ± 12.01
Gender, female/male, n	29/207
Alcohol abuse, yes/no, n	133/103
Cirrhosis, yes/no, n	211/25
HBsAg, negative/positive, n	34/202
ICAM-1	984.32 ± 370.48
AFP (ng/mL)	1809.97 ± 5533.23
WBC (109/L)	6.35 ± 2.37
Platelets (109/L)	175.65 ± 78.02
Albumin (g/L)	40.67 ± 4.61
TBIL(μmol/L)	18.52 ± 24.98
ALT (U/L)	50.27 ± 47.91
AST (U/L)	63.78 ± 86.73
NLR	2.83 ± 2.01
γ-GT (U/L)	117.55 ± 108.79

HBsAg: Hepatitis B surface antigen; ICAM-1: Intercellular adhesion molecule-1; AFP: Alpha-fetoprotein; WBC: White blood cell; TBIL: Total bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; NLR: Neutrophil-to-lymphocyte ratio; γ-GT: γ-glutamyl transpeptidase.

Table 2 Correlation between the clinicopathological variables and serum intercellular adhesion molecule-1 level in hepatocellular carcinoma n (%)

Clinical character	Variable	Number of patients	ICAM-1 level		χ2	P value
			Low1	High2
Age (yr)	≤ 55	161	37 (23.0)	124 (77.0)	0.265	0.607
	> 55	75	15 (20.0)	60 (80.0)
Gender	Male	207	44 (21.3)	163 (78.7)	0.593	0.441
	Female	29	8 (27.6)	21 (72.4)
Family history	No	203	42 (20.7)	161 (79.3)	1.527	0.217
	Yes	33	10 (30.3)	23 (69.7)
HBsAg	Negative	34	7 (20.6)	27 (79.4)	0.048	0.826
	Positive	202	45 (22.3)	157 (77.7)
AFP (ng/mL)	≤ 100	99	29 (29.3)	70 (70.7)	5.231	0.022
	> 100	137	23 (16.8)	114 (83.2)
Median size (cm)	≤ 5	32	9 (28.1)	23 (71.9)	0.800	0.371
	> 5	204	43 (21.1)	161 (78.9)
Cirrhosis	No	25	2 (8.0)	23 (92.0)	3.206	0.073
	Yes	211	50 (23.7)	161 (76.3)
Tumor number	Single	149	37 (24.8)	112 (75.2)	1.842	0.175
	Multiple	87	15 (17.2)	72 (82.8)
NLR	≤ 2.31	130	31 (23.8)	99 (76.2)	0.553	0.457
	> 2.31	106	21 (19.8)	85 (80.2)
TNM stage	I-II	108	37 (34.3)	71 (65.7)	17.324	< 0.001
	III-IV	128	15 (11.7)	113 (88.3)
PVTT	No	184	48 (26.1)	136 (73.9)	7.985	0.005
	Yes	52	4 (7.7)	48 (92.3)
Distant metastasis	No	217	52 (24.0)	165 (76.0)	5.840	0.016
	Yes	19	0 (0)	19 (100)
Recurrence	No	139	24 (17.3)	115 (82.7)	4.475	0.034
	Yes	97	28 (28.9)	69 (71.1)

¹Low, ICAM-1 ≤ 684 ng/mL;

²High, ICAM-1 > 684 ng/mL. HBsAg: Hepatitis B surface antigen; ICAM-1: Intercellular adhesion molecule-1; AFP: Alpha-fetoprotein; NLR: Neutrophil-to-lymphocyte ratio; TNM: Tumor-node-metastasis; PVTT: Portal vein tumor thrombus.

Table 3 Association between intercellular adhesion molecule-1 level, clinical parameters and disease-free survival/overall survival

Clinical character	Category	Number of patients	Disease-free survival (mo)			Overall survival (mo)
			mean	95%CI	P value	mean	95%CI	P value
ICAM-1 (ng/mL)	≤ 684	52	58.18	44.77-71.58	0.003	64.57	52.14-77.01	0.002
	> 684	184	36.96	30.51-43.40		42.75	36.48-49.01
Age (yr)	≤ 55	161	40.37	33.32-47.43	0.325	45.89	39.05-52.74	0.262
	> 55	75	45.38	34.62-56.14		51.57	41.37-61.77
Gender	Female	29	57.84	38.90-76.78	0.066	62.96	43.72-82.19	0.076
	Male	207	39.73	33.60-45.86		44.66	38.58-50.74
Family history	No	203	39.83	33.62-46.05	0.077	45.69	39.68-51.69	0.092
	Yes	33	53.83	37.30-70.36		59.63	43.90-75.36
HBsAg	Negative	34	47.54	30.65-64.43	0.501	52.62	36.64-68.60	0.462
	Positive	202	40.74	34.47-47.01		46.72	40.65-52.79
AFP (ng/mL)	≤ 100	99	46.01	36.52-55.49	0.286	52.18	43.07-61.28	0.214
	> 100	137	39.00	31.53-46.47		44.75	37.51-51.99
Tumor size (cm)	≤ 5	32	70.51	53.82-87.19	< 0.001	77.42	62.56-92.28	< 0.001
	> 5	204	37.57	31.49-43.66		43.36	37.44-49.28
Cirrhosis	No	25	34.60	17.57-51.64	0.190	39.16	22.83-55.49	0.237
	Yes	211	42.81	36.53-49.09		48.83	42.77-54.89
Tumor number	Single	149	50.25	42.28-58.21	< 0.001	55.27	47.66-62.87	< 0.001
	Multiple	87	27.72	20.32-35.12		34.92	27.37-42.48
NLR	≤ 2.31	130	53.58	45.00-62.17	< 0.001	59.00	50.88-67.12	< 0.001
	> 2.31	106	27.50	20.58-34.43		34.23	27.17-41.29
TNM stage	I-II	108	59.65	50.13-69.18	< 0.001	66.86	58.17-75.54	< 0.001
	III-IV	128	27.17	20.87-33.46		31.88	25.56-38.21
PVTT	No	184	47.62	40.59-54.64	< 0.001	54.25	47.61-60.90	< 0.001
	Yes	52	22.06	13.88-30.24		24.73	16.55-32.91
Distant metastasis	No	217	42.85	36.62-49.08	0.313	48.89	42.90-54.88	0.166
	Yes	19	26.79	14.76-38.82		31.21	18.29-44.13
Recurrence	No					44.59	36.73-52.46	0.051
	Yes					51.58	43.77-59.39

ICAM-1: Intercellular adhesion molecule-1; HBsAg: Hepatitis B surface antigen; AFP: Alpha-fetoprotein; NLR: Neutrophil-to-lymphocyte ratio; TNM: Tumor-node-metastasis; PVTT: Portal vein tumor thrombus.

Table 4 Cox multivariate proportional hazard model of independent predictors on disease-free and overall survival

Variable	Disease-free survival		Overall survival
	HR (95%CI)	P value	HR (95%CI)	P value
ICAM-1 (ng/mL) (> 684 vs ≤ 684)	1.643 (1.125-2.401)	0.010	1.692 (1.152-2.486)	0.007
Tumor number (multiple vs single)	1.324 (0.902-1.944)	0.152	1.273 (0.924-1.755)	0.140
TNM stage (III-IV vs  I-II)	1.390 (0.931-2.077)	0.108	1.468 (1.074-2.015)	0.016
PVTT (yes vs no)	1.397 (1.016-1.920)	0.040	1.514 (1.031-2.225)	0.035
Tumor size (cm) (> 5 vs ≤ 5)	0.666 (0.389-1.149)	0.144	1.551 (0.899-2.656)	0.115
NLR (> 2.31 vs ≤ 2.31)	1.578 (1.156-2.153)	0.004	1.485 (1.086-2.030)	0.013

ICAM-1: Intercellular adhesion molecule-1; TNM: Tumor-node-metastasis; PVTT: Portal vein tumor thrombus; NLR: Neutrophil-to-lymphocyte ratio.