血清甲胎蛋白、白细胞介素-6和高尔基体蛋白73在肝脏疾病中的表达特点及其对肝细胞癌的诊断价值

doi:10.3877/cma.j.issn.1674-1358.2017.04.006

目的

探讨血清甲胎蛋白（AFP）、白细胞介素-6（IL-6）和高尔基体蛋白73（GP73）在肝病中的表达特点及对HBV相关原发性肝癌（PHC）的临床诊断价值。

方法

选择2015年1月至2016年3月于解放军第一八〇医院肝病中心住院的慢性HBV感染者共391例为研究对象，采用全自动电化学发光免疫分析仪和酶联免疫法分别检测患者血清AFP、IL-6与GP73的表达水平，分析这3种血清标志物对PHC的诊断价值。

结果

CHB、乙型肝炎肝硬化（HLC）、PHC三组人群中，血清IL-6和GP73水平随病情加重而逐渐升高（P均< 0.05），失代偿期HLC组血清IL-6和GP73水平显著高于代偿期组（P均< 0.001），AFP表达水平于PHCⅡ期、Ⅲ期患者中显著升高（Z = 3.305、P = 0.001，Z = 2.902、P = 0.003），血清IL-6和GP73水平随肝细胞癌等级升高而升高（P均< 0.05）。血清IL-6与GP73呈对数正相关（r = 0.553，P < 0.001）。3种血清标志物诊断PHC的曲线下面积分别为0.788、0.787和0.649。AFP + IL-6联合患者组曲线下面积为0.873，敏感性显著升高，与AFP相比差异具有统计学意义（χ² = 49.891、P < 0.001）。AFP + IL-6 + GP73联合组与AFP + IL-6联合组诊断价值差异无统计学意义（Z = 1.256、P = 0.209）。IL-6与GP73对失代偿期肝硬化和肝细胞癌的鉴别诊断价值不高，曲线下面积均低于0.6。

结论

IL-6可作为AFP诊断肝癌的补充预测因子，而GP73对肝癌的诊断价值不高。

关键词: 失代偿期肝硬化, 肝癌, 甲胎蛋白, 白细胞介素-6, 高尔基体蛋白73

Objective

To investigate the pattern of serum α-fetal protein (AFP), intereleukin-6 (IL-6) and Golgi protein 73 (GP73) expressed in liver diseases and the diagnostic value on hepatitis B virus related primary hepatic carcinoma (PHC).

Methods

Total of 391 patients with HBV in the 180th Hospital of PLA, from January 2015 to March 2016 were collected. AFP and IL-6 were detected by automatic electrochemical luminescence immunity analyzer. GP73 was detected by ELISA. Their diagnostic value for the PHC were analyzed by ROC analysis.

Results

Among chronic hepatitis B (CHB) group, HLC group and PHC group, the level of serum IL-6 and GP73 significantly increased when the disease worsened (P < 0.05). Compared with the compensated HLC group, the serum level of them showed higher in decompensated group (P < 0.001). The expression of AFP were significantly increased in stage Ⅱ and Ⅲ of PHC compared with stage Ⅰ (Z = 3.305, P = 0.001; Z = 2.902, P = 0.003). The level of serum IL-6 and GP73 significantly increased when the stage of PHC rising (P < 0.05). There was positive logarithmic correlation between IL-6 and GP73 (r = 0.553, P < 0.001). The area under the ROC curve of AFP, IL-6 and GP73 for diagnosing PHC were 0.788, 0.787 and 0.649, respectively. When taking AFP and IL-6 as predictors together, the area was 0.873 and the sensitivity was significantly higher than AFP (χ ²= 49.891, P < 0.001). There was no difference between combined group of AFP + IL-6 + GP73 and AFP + IL-6 in diagnosing PHC (Z = 1.256, P = 0.209). IL-6 and GP73 could not distinguish decompensated HLC from hepatocellular carcinoma, their area under the ROC curve were both less than 0.6.

Conclusions

AFP and IL-6 could serve as a complementary factor to predict the occurrence of PHC, while the value of GP73 in diagnosing PHC was not high.

Key words: Decompensated hepatitic B liver cirrhosis, Hepatocellular carcinoma, α-fetal protein, Interleukin 6, Golgi protein 73

表1 血清AFP、IL-6和GP73在不同肝脏疾病患者中的表达

组别	例数	AFP [M（QR），ng/ml]	IL-6 [M（QR），pg/ml]	GP73（ ± s，ng/ml）
CHB患者	140	4.91（12.37）	2.03（32.77）	114.20 ± 73.94
HLC患者	129	5.10（13.52）	11.07（25.31）	180.20 ± 90.32
PHC患者	122	193.90（9 762.08）	26.90（60.96）	204.00 ± 113.70
^a统计量		Z = 0.147	Z = 9.653	t = 6.573
^aP		0.883	< 0.001	< 0.001
^b统计量		Z = 8.081	Z = 11.977	t = 8.465
^bP		< 0.001	< 0.001	< 0.001
^c统计量		Z = 7.820	Z = 4.691	t = 1.849
^cP		< 0.001	< 0.001	0.048

表1 血清AFP、IL-6和GP73在不同肝脏疾病患者中的表达

组别	例数	AFP [M（QR），ng/ml]	IL-6 [M（QR），pg/ml]	GP73（ ± s，ng/ml）
CHB患者	140	4.91（12.37）	2.03（32.77）	114.20 ± 73.94
HLC患者	129	5.10（13.52）	11.07（25.31）	180.20 ± 90.32
PHC患者	122	193.90（9 762.08）	26.90（60.96）	204.00 ± 113.70
^a统计量		Z = 0.147	Z = 9.653	t = 6.573
^aP		0.883	< 0.001	< 0.001
^b统计量		Z = 8.081	Z = 11.977	t = 8.465
^bP		< 0.001	< 0.001	< 0.001
^c统计量		Z = 7.820	Z = 4.691	t = 1.849
^cP		< 0.001	< 0.001	0.048

表2 血清AFP、IL-6和GP73在HLC患者与PHC患者中的表达

组别		例数	AFP[M（QR），ng/ml]	IL-6[M（QR），pg/ml]	GP73（ ± s，ng/ml）
HLC患者
	代偿期	33	6.12（17.77）	2.76（92.30）	129.70 ± 77.55
	失代偿期	96	5.02（11.80）	13.95（453.86）	197.50 ± 88.19
PHC患者
	Ⅰ期	9	2.64（18.24）	7.47（112.81）	129.00 ± 78.22
	Ⅱ期	48	219.90（6 468.93）	10.39（1 263.67）	162.80 ± 98.59
	Ⅲ期	65	240.90（25 751.20）	39.59（730.51）	244.80 ± 113.00
^a统计量			Z = 1.400	Z = 4.984	t = 3.923
^aP			0.161	< 0.001	< 0.001
^b统计量			Z = 3.305	Z = 1.852	t = 1.969
^bP			0.001	0.044	0.037
^c统计量			Z = 2.902	Z = 2.109	t = 2.966
^cP			0.003	0.035	0.004
^d统计量			Z = 0.168	Z = 3.351	t = 4.020
^dP			0.866	< 0.001	< 0.001

表2 血清AFP、IL-6和GP73在HLC患者与PHC患者中的表达

组别		例数	AFP[M（QR），ng/ml]	IL-6[M（QR），pg/ml]	GP73（ ± s，ng/ml）
HLC患者
	代偿期	33	6.12（17.77）	2.76（92.30）	129.70 ± 77.55
	失代偿期	96	5.02（11.80）	13.95（453.86）	197.50 ± 88.19
PHC患者
	Ⅰ期	9	2.64（18.24）	7.47（112.81）	129.00 ± 78.22
	Ⅱ期	48	219.90（6 468.93）	10.39（1 263.67）	162.80 ± 98.59
	Ⅲ期	65	240.90（25 751.20）	39.59（730.51）	244.80 ± 113.00
^a统计量			Z = 1.400	Z = 4.984	t = 3.923
^aP			0.161	< 0.001	< 0.001
^b统计量			Z = 3.305	Z = 1.852	t = 1.969
^bP			0.001	0.044	0.037
^c统计量			Z = 2.902	Z = 2.109	t = 2.966
^cP			0.003	0.035	0.004
^d统计量			Z = 0.168	Z = 3.351	t = 4.020
^dP			0.866	< 0.001	< 0.001

图1 血清IL-6与GP73的相关性

表3 AFP、GP73和IL-6对PHC的诊断价值分析

标志物	AUC	Z值	^aP值	临界值	敏感性（%）	特异性（%）	准确性（%）
AFP	0.788	10.041	< 0.001	84.77 ng/ml	59.02	94.05	83.12
IL-6	0.787	12.156	< 0.001	5.58 pg/ml	84.43	63.57	70.08
GP73	0.649	4.937	< 0.001	229.22 ng/ml	40.98	81.04	68.54
AFP + IL-6	0.873	19.537	< 0.001	—	81.97	75.09	77.23
AFP + IL-6 + GP73	0.881	20.490	< 0.001	—	75.41	85.13	82.10

表3 AFP、GP73和IL-6对PHC的诊断价值分析

标志物	AUC	Z值	^aP值	临界值	敏感性（%）	特异性（%）	准确性（%）
AFP	0.788	10.041	< 0.001	84.77 ng/ml	59.02	94.05	83.12
IL-6	0.787	12.156	< 0.001	5.58 pg/ml	84.43	63.57	70.08
GP73	0.649	4.937	< 0.001	229.22 ng/ml	40.98	81.04	68.54
AFP + IL-6	0.873	19.537	< 0.001	—	81.97	75.09	77.23
AFP + IL-6 + GP73	0.881	20.490	< 0.001	—	75.41	85.13	82.10

表4 AFP、GP73和IL-6对失代偿期HLC与PHC的鉴别诊断

标志物	AUC	Z值	^aP值	临界值	敏感性（%）	特异性（%）	准确性（%）
AFP	0.797	9.913	<0.001	29.44 ng/ml	64.75	88.54	75.22
IL-6	0.568	1.721	0.085	21.80 pg/ml	56.56	64.58	60.09
GP73	0.505	0.139	0.889	146.62 ng/ml	40.16	67.71	52.29

表4 AFP、GP73和IL-6对失代偿期HLC与PHC的鉴别诊断

标志物	AUC	Z值	^aP值	临界值	敏感性（%）	特异性（%）	准确性（%）
AFP	0.797	9.913	<0.001	29.44 ng/ml	64.75	88.54	75.22
IL-6	0.568	1.721	0.085	21.80 pg/ml	56.56	64.58	60.09
GP73	0.505	0.139	0.889	146.62 ng/ml	40.16	67.71	52.29

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Pattern of serum α-fetal protein, intereleukin-6 and Golgi protein 73 expressed in liver diseases and their diagnostic value on hepatocellular carcinoma

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Pattern of serum α-fetal protein, intereleukin-6 and Golgi protein 73 expressed in liver diseases and their diagnostic value on hepatocellular carcinoma