Neuron-glial antigen 2 overexpression in hepatocellular carcinoma predicts poor prognosis

Table 1 Relationship between neuron-glial antigen 2 expression and clinicopathological characteristics of hepatocellular carcinoma patients

Characteristic	n	NG2		χ2	P value
		High	Low
Hepatocellular carcinoma	132	84	48		< 0.0001
Non-tumor liver	96	27	69
Total cases	132	84	48
Age (yr)
≥ 50	62	40	22	0.039	0.843
< 50	70	44	26
Sex
Male	106	69	37	0.494	0.482
Female	26	15	11
Tumor size
≥ 5 cm	90	56	34	0.244	0.621
< 5 cm	42	28	14
TNM stage
I, II	52	25	27	8.976	0.002
III, IV	80	59	21
Tumor differentiation
Well	33	15	18	9.436	0.008
Moderate	52	32	20
Poor	47	37	10
Serum AFP
≥ 200 ng/dL	42	30	12	1.616	0.203
< 200 ng/dL	90	54	36
Recurrence
Yes	65	48	17	5.769	0.016
No	67	36	31
Invasion
Yes	70	51	19	5.476	0.019
No	62	33	29
Tumor number
Multiple	31	19	12	0.096	0.756
Single	101	65	36
Tumor capsule
Yes	58	33	25	2.031	0.154
No	74	51	23

AFP: Alpha fetoprotein; NG2: Neuron-glia antigen 2; HCC: Hepatocellular carcinoma; TNM stage: Tumor node metastasis stage.

Table 2 Immunohistochemical scoring system

	Score
Percent positive
0%	0
1%-10%	1
11%-50%	2
51%-80%	3
> 80%	4
Staining intensity
No staining	0
Weakly stained	1
Moderately stained	2
Strongly stained	3

The neuron-glial antigen 2 (NG2) expression score was calculated by multiplying the percent positive score by the staining intensity score; these scores ranged from 0-12. The tumors were divided into the following groups: negative (-, score of 0), low expression (1+, scores 1-4), moderate expression (2+, scores 5-8), and strong expression (3+, scores 9-12). The NG2 immunohistochemistry results were used to divide the samples into two groups: low expression (0 and 1+) and high expression (2+ and 3+).

Table 3 Univariate analysis of prognostic factors for disease-free survival and overall survival in 132 patients with hepatocellular carcinoma

Factor	n	6-yr disease-free survival	P value	6-yr overall survival	P value
NG2			0.000		0.000
Negative	84	15.2%		29.2%
Positive	48	6.7%		9.5%
Age (yr)			0.946		0.356
≥ 50	62	10.2%		21.0%
< 50	70	9.7%		31.4%
Sex			0.281		0.316
Male	106	7.1%		23.6%
Female	26	21.7%		38.5%
Tumor size			0.122		0.116
≥ 5 cm	90	11.8%		28.9%
< 5 cm	42	5.6%		21.4%
TNM stage			0.001		0.003
I, II	52	10.2%		34.6%
III, IV	80	9.7%		21.3%
Differentiation			0.108		0.119
Well	33	23.3%		33.3%
Moderate	52	2.0%		9.6%
Poor	47	9.5%		12.8%
Serum AFP			0.044		0.099
≥ 200 ng/dL	42	2.3%		18.0%
< 200 ng/dL	90	13.6%		14.0%
Invasion			0.000		0.000
Yes	70	7.7%		12.9%
No	62	12.5%		21.0%
Number			0.041		0.057
Multiple	31	10.7%		16.1%
Single	101	9.7%		16.8%
Capsule			0.064		0.055
Yes	58	14.3%		21.6%
No	74	6.2%		32.8%

NG2: Neuron-glia antigen 2; TNM stage: Tumor node metastasis stage.

Table 4 Multivariate analysis of individual parameters correlating with overall survival and disease-free survival

Variable	Overall survival			Disease-free survival
	HR	(95%CI)	P value	HR	(95%CI)	P value
TNM stage	2.039	(1.329-3.130)	0.001	2.078	(1.347-3.206)	0.001
Serum AFP	1.903	(1.247-2.903)	0.003	1.767	(1.163-2.685)	0.008
Tumor capsule	-	-	-	0.652	(0.429-0.991)	0.045
Invasion	1.938	(1.273-2.950)	0.002	1.941	(1.265-2.980)	0.002
NG2	2.035	(1.302-3.179)	0.002	1.974	(1.258-3.097)	0.003

TNM stage: Tumor node metastasis stage; AFP: Alpha fetoprotein; NG2: Neuron-glia antigen 2.