血清高尔基体蛋白73、缺氧诱导因子-1α及基质金属蛋白酶-9对乙型肝炎病毒相关肝细胞癌经导管肝动脉化疗栓塞治疗效果的预测价值

包依夏姆·阿巴拜克力; 张洁; 徐琴; 鲁晓擘; 朱帝文

doi:10.12449/JCH260616

血清高尔基体蛋白73、缺氧诱导因子-1α及基质金属蛋白酶-9对乙型肝炎病毒相关肝细胞癌经导管肝动脉化疗栓塞治疗效果的预测价值

DOI: 10.12449/JCH260616

1.
新疆医科大学第一附属医院感染病·肝病中心，乌鲁木齐 830000
2.
新疆医科大学第一附属医院介入放射科，乌鲁木齐 830000

基金项目:

新疆维吾尔自治区自然科学基金面上项目 (2022D01C490)

伦理学声明：本研究于2022年1月经由新疆医科大学第一附属医院伦理委员会审批通过，批号：新医大一附院伦审［2022］490号。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：包依夏姆・阿巴拜克力负责课题设计，资料分析，论文撰写；张洁、徐琴负责临床资料收集，实验操作；鲁晓擘负责实验设计与质量控制；朱帝文负责课题指导，论文修改与定稿。

详细信息

通信作者:
朱帝文， steven9330@163.com （ORCID： 0000-0002-1259-7516）

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出版历程
- 收稿日期: 2026-01-15
- 录用日期: 2026-03-12
- 出版日期: 2026-06-25

Value of serum Golgi protein 73， hypoxia-inducible factor-1α， and matrix metalloproteinase-9 in predicting the efficacy of transcatheter arterial chemoembolization in treatment of hepatitis B virus-related hepatocellular carcinoma

1.
Infection and Liver Disease Center，The First Affiliated Hospital of Xinjiang Medical University，Urumqi 830000，China
2.
Department of Interventional Radiology，The First Affiliated Hospital of Xinjiang Medical University，Urumqi 830000，China

Research funding:

General Program of the Natural Science Foundation of Xinjiang Uygur Autonomous Region (2022D01C490)

More Information

Corresponding author: ZHU Diwen， steven9330@163.com （ORCID： 0000-0002-1259-7516）

摘要

摘要: 目的探讨乙型肝炎病毒（HBV）相关肝细胞癌（HCC）患者经导管动脉化疗栓塞术（TACE）治疗前后血清高尔基体蛋白73（GP73）、缺氧诱导因子-1α（HIF-1α）及基质金属蛋白酶-9（MMP-9）水平与疗效的关系。方法选取2023年1月—2025年10月在新疆医科大学第一附属医院首次接受TACE治疗的135例HBV相关HCC患者为研究对象，分别于TACE术前及术后1个月检测患者血清GP73、HIF-1α及MMP-9水平，术后根据疗效将患者分为缓解组与未缓解组。比较两组患者一般资料、治疗前后血清GP73、HIF-1α及MMP-9水平，采用Logistic回归分析TACE疗效的影响因素，采用受试者操作特征（ROC）曲线评估治疗前GP73、HIF-1α、MMP-9及其联合对TACE疗效的预测价值。计量资料两组间比较采用成组t检验，计数资料两组间比较采用χ²检验。结果治疗后，135例患者中缓解组78例（57.78%），未缓解组57例（42.22%）。治疗前，缓解组患者血清GP73、HIF-1α和MMP-9水平均显著低于未缓解组（P值均<0.05）；治疗后，两组血清GP73、HIF-1α、MMP-9水平均较治疗前有所降低，且缓解组显著低于未缓解组（P值均<0.05）。二元Logistic回归分析显示，治疗前血清GP73、HIF-1α和MMP-9水平升高是影响TACE疗效的独立危险因素（P值均<0.05）。ROC曲线分析结果显示，治疗前血清GP73、HIF-1α和MMP-9水平单独预测TACE疗效的曲线下面积（AUC）分别为0.799、0.835和0.777，其中HIF-1α的预测价值最高；三者联合检测的AUC为0.950，约登指数为0.787，最佳临界值为0.39，敏感度为87.72%，特异度为91.03%。结论 TACE治疗可降低HBV相关HCC患者血清GP73、HIF-1α及MMP-9水平，且疗效良好的患者下降更为显著。治疗前高水平的血清GP73、HIF-1α及MMP-9是TACE近期疗效不佳的独立危险因素，三者联合检测对TACE疗效具有较高的预测价值。
- 乙型肝炎病毒 /
- 癌，肝细胞 /
- 经导管动脉化疗栓塞术 /
- 高尔基体蛋白73 /
- 缺氧诱导因子1， α亚基 /
- 基质金属蛋白酶9
Abstract: Objective To investigate the association of the serum levels of Golgi protein 73 （GP73）， hypoxia-inducible factor-1α （HIF-1α）， and matrix metalloproteinase-9 （MMP-9） before and after transcatheter arterial chemoembolization （TACE） with the treatment outcome of patients with hepatitis B virus （HBV）-related hepatocellular carcinoma （HCC）. Methods A total of 135 patients with HBV-related HCC who received TACE for the first time in The First Affiliated Hospital of Xinjiang Medical University from January 2023 to October 2025 were enrolled as subjects， and the serum levels of GP73， HIF-1α， and MMP-9 were measured before TACE and at 1 month after TACE. According to the treatment outcome after TACE， the patients were divided into remission group and non-remission group. The two groups were compared in terms of general information and the serum levels of GP73， HIF-1α， and MMP-9 before and after treatment. The Logistic regression analysis was used to investigate the influencing factors for the efficacy of TACE， and the receiver operating characteristic （ROC） curve was used to assess the value of the serum levels of GP73， HIF-1α， and MMP-9 before treatment used alone or in combination in predicting the efficacy of TACE. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. Results Among the 135 patients after treatment， 78 （57.78%） were enrolled in the remission group and 57 （42.22%） were enrolled in the non-remission group. Before treatment， the remission group had significantly lower serum levels of GP73， HIF-1α， and MMP-9 than the non-remission group （all P<0.05）； after treatment， both groups had reductions in the serum levels of GP73， HIF-1α， and MMP-9， and the remission group had significantly lower levels than the non-remission group （all P<0.05）. The binary Logistic regression analysis showed that increases in the serum levels of GP73， HIF-1α， and MMP-9 before treatment were independent influencing factors for the efficacy of TACE （all P<0.05）. The ROC curve analysis showed that the serum levels of GP73， HIF-1α， and MMP-9 before treatment used alone had an area under the ROC curve （AUC） of 0.799， 0.835， and 0.777， respectively， in predicting the efficacy of TACE， among which HIF-1α showed the highest predictive value， and the combination of these three indicators had an AUC of 0.950， a Youden index of 0.787， an optimal cut-off value of 0.39， a sensitivity of 87.72%， and a specificity of 91.03%. Conclusion TACE can reduce the serum levels of GP73， HIF-1α， and MMP-9 in patients with HBV-related HCC， and patients with a good outcome tend to have greater reductions. The high serum levels of GP73， HIF-1α， and MMP-9 before treatment are independent risk factors for poor short-term efficacy of TACE， and the combination of these three indicators has a relatively high value in predicting the efficacy of TACE.
- Hepatitis B Virus /
- Carcinoma， Hepatocellular /
- Transcatheter Arterial Chemoembolization /
- Golgi Protein 73 /
- Hypoxia-Inducible Factor 1， alpha Subunit /
- Matrix Metalloproteinase 9

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注： GP73，高尔基体蛋白73；HIF-1α，缺氧诱导因子-1α；MMP-9，基质金属蛋白酶-9；TACE，经导管动脉化疗栓塞术。

图 1 血清GP73、HIF-1α、MMP-9水平对TACE疗效预测价值的受试者操作特征曲线

Figure 1. ROC curves for predicting TACE efficacy based on serum GP73， HIF-1α， and MMP-9 levels

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表 1 两组患者一般资料比较

Table 1. Comparison of general data between the two groups

指标	缓解组（n=78）	未缓解组（n=57）	统计值	P值
年龄（岁）	56.32±9.36	57.14±8.41	t=0.524	0.601
性别［例（%）］			χ²=0.187	0.665
男	60（76.92）	42（73.68）
女	18（23.08）	15（26.32）
病程（年）	2.89±0.52	2.92±0.48	t=0.342	0.733
肿瘤大小（cm）	6.53±2.14	6.82±2.26	t=0.759	0.449
Child-Pugh分级［例（%）］			χ²=0.863	0.353
A级	59（75.64）	39（68.42）
B级	19（24.36）	18（31.58）
BCLC分期［例（%）］			χ²=0.318	0.573
B期	50（64.10）	32（56.14）
C期	28（35.90）	25（43.86）
注：Child-Pugh分级，蔡尔德-皮尤分级；BCLC分期，巴塞罗那肝癌临床分期。

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表 2 两组患者治疗前后血清GP73、HIF-1α和MMP-9水平比较

Table 2. Comparison of serum GP73， HIF-1α and MMP-9 levels between the two groups before and after treatment

组别	例数	GP73（ng/mL）		HIF-1α（ng/L）		MMP-9（ng/mL）
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
缓解组	78	86.46±13.26	51.23±10.14	75.85±8.39	60.25±7.56	215.25±45.14	146.85±38.56
未缓解组	57	108.54±22.14	96.25±13.52	88.54±9.25	79.52±8.55	265.14±52.36	235.24±47.85
t值		7.218	22.114	8.311	13.837	5.926	11.874
P值		<0.001	<0.001	<0.001	<0.001	<0.001	<0.001
注：GP73，高尔基体蛋白73；HIF-1α，缺氧诱导因子-1α；MMP-9，基质金属蛋白酶-9。

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表 3 影响TACE疗效的多因素分析

Table 3. Multiplicity analysis of factors influencing the efficacy of TACE

指标	β值	SE	Wald	P值	OR	95%CI
GP73（ng/mL）	0.067	0.018	13.814	<0.001	1.069	1.032～1.107
HIF-1α（ng/L）	0.220	0.047	22.117	<0.001	1.246	1.137～1.365
MMP-9（ng/mL）	0.028	0.007	15.556	<0.001	1.028	1.014～1.042
注：GP73，高尔基体蛋白73；HIF-1α，缺氧诱导因子-1α；MMP-9，基质金属蛋白酶-9；TACE，经导管动脉化疗栓塞术；SE，标准误；OR，比值比；CI，置信区间。

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表 4 治疗前血清GP73、HIF-1α和MMP-9水平对TACE疗效的预测价值分析

Table 4. Predictive value of serum GP73， HIF-1α， and MMP-9 levels before treatment for TACE efficacy

指标	AUC（95%CI）	Z值	P值	约登指数	最佳临界值	敏感度（%）	特异度（%）
GP73	0.799（0.722～0.863）	7.206	<0.001	0.547	100.93 ng/mL	64.91	89.74
HIF-1α	0.835（0.761～0.893）	9.778	<0.001	0.520	86.03 ng/L	59.65	95.31
MMP-9	0.777（0.697～0.844）	6.489	<0.001	0.534	261.29 ng/mL	64.91	88.46
联合检测	0.950（0.898～0.980）	27.775	<0.001	0.787	0.39	87.72	91.03
注：GP73，高尔基体蛋白73；HIF-1α，缺氧诱导因子-1α；MMP-9，基质金属蛋白酶-9；TACE，经导管动脉化疗栓塞术；AUC，曲线下面积；CI，置信区间。

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