血清甲胎蛋白联合碱性磷酸酶评分对可切除肝细胞癌患者预后的预测价值

卢晶; 张雅敏; 李华; 缪妍

doi:10.3969/j.issn.1001-5256.2023.03.017

血清甲胎蛋白联合碱性磷酸酶评分对可切除肝细胞癌患者预后的预测价值

DOI: 10.3969/j.issn.1001-5256.2023.03.017

卢晶^{1, 2},
张雅敏^3, , ,,
李华²,
缪妍⁴

1.
天津医科大学一中心临床学院，天津 300192
2.
保定市第一医院肿瘤科，河北保定 071000
3.
天津市第一中心医院肝胆外科，天津 300192
4.
保定市第一中心医院麻醉科，河北保定 071000

基金项目:

天津市科技计划项目 (19ZXDBSY00010);

保定市科技计划项目 (2241ZF219)

伦理学声明：本研究方案于2016年1月3日经由天津市第一中心医院伦理委员会审批，批号：YJDYYY-2016007，所纳入患者均签署知情同意书。

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：卢晶负责课题设计，拟定写作思路，资料分析，撰写论文并最后定稿；李华、缪妍参与收集数据，修改论文；张雅敏负责文章指导，并最终定稿。

详细信息

通信作者:
张雅敏，13802122219@163.com(ORCID: 0000-0002-3724-6907)

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出版历程
- 收稿日期: 2022-08-02
- 录用日期: 2022-09-12
- 出版日期: 2023-03-20

Value of a scoring system based on the serum levels of alpha-fetoprotein and alkaline phosphatase in predicting the prognosis of patients with resectable hepatocellular carcinoma

Jing LU^{1, 2},
Yamin ZHANG^{3
, ,
,},
Hua LI²,
Yan MIAO⁴

1.
The First Central Clinical College of Tianjin Medical University, Tianjin 300192, China
2.
Department of Oncology, Baoding First Hospital, Baoding, Hebei 071000, China
3.
Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300192, China
4.
Department of Anesthesiology, Baoding First Central Hospital, Baoding, Hebei 071000, China

Research funding:

Tianjin Science and Technology Plan Project (19ZXDBSY00010);

Baoding Science and Technology Plan Project (2241ZF219)

More Information

Corresponding author: ZHANG Yamin, 13802122219@163.com (ORCID: 0000-0002-3724-6907)

摘要

摘要: 目的建立一个基于术前血清甲胎蛋白(AFP)与碱性磷酸酶(ALP)的评分系统，并探讨其在可切除肝细胞癌(HCC)患者中的预后价值。方法回顾性纳入2016年1月—2019年8月在天津市第一中心医院以肝切除术作为初始治疗的154例HCC患者。通过受试者工作特征(ROC)曲线确定血清AFP与ALP的最佳临界值。采用Kaplan-Meier曲线和Log-rank检验进行生存分析，以评估AFP联合ALP评分与HCC患者无病生存(DFS)的关系。通过单因素及多因素Cox回归分析确定HCC患者的独立预后因素。符合正态分布的计量资料组间比较采用独立样本t检验；不符合正态分布的计量资料组间比较采用Mann-Whitney U检验。计数资料组间比较采用χ²检验。结果 ROC曲线显示，血清AFP预测DFS的最佳临界值为250.0 ng/mL，曲线下面积(AUC)为0.674 (95%CI：0.580~0.767)；血清ALP的最佳临界值为95.5 U/L, AUC为0.745 (95%CI：0.652~0.838)。生存分析结果展示术前血清高AFP(≥250.0 ng/mL)和高ALP(≥95.5 U/L)均与HCC患者不良预后显著相关(P值均＜0.001)。AFP联合ALP评分进一步将HCC患者分为0分(AFP＜250.0 ng/mL且ALP＜95.5 U/L)、1分(AFP≥250.0 ng/mL，ALP＜95.5 U/L或AFP＜250.0 ng/mL，ALP≥95.5 U/L)和2分(AFP≥250.0 ng/mL且ALP≥95.5 U/L)共3个研究组。生存曲线展示0分、1分和2分组患者的中位DFS分别为60.0(56.7~67.3)个月、20.0(1.4~36.6)个月和13.0(7.9~18.0)个月，组间生存差异均有统计学意义(P值均＜0.05)。血清AFP联合ALP评分(1分vs 0分：HR=4.060, 95%CI: 2.050~8.039，P＜0.001；2分vs 0分：HR=4.583, 95%CI: 2.385~8.805，P＜0.001)是HCC患者的独立预后因素。结论基于血清AFP与ALP的联合评分能够有效识别预后不良的HCC患者，可作为HCC临床治疗中一项简便、可靠的预后评估工具。
- 癌, 肝细胞 /
- 甲胎蛋白类 /
- 碱性磷酸酶 /
- 预后
Abstract: Objective To establish a scoring system based on the preoperative serum levels of alpha-fetoprotein (AFP) and alkaline phosphatase (ALP), and to investigate its value in predicting the prognosis of patients with resectable hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for 154 HCC patients who underwent hepatectomy as the initial treatment in Tianjin First Central Hospital from January 2016 to August 2019. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values of serum AFP and ALP; the Kaplan-Meier curve and the log-rank test were used for survival analysis to evaluate the relationship between the AFP-ALP score and disease-free survival (DFS); univariate and multivariate Cox regression analyses were used to identify the independent prognostic factors for HCC patients. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. Results The ROC curve analysis showed that serum AFP had an optimal cut-off value of 250.0 ng/mL and an area under the ROC curve (AUC) of 0.674 (95% confidence interval [CI]: 0.580-0.767) in predicting DFS, while serum ALP had an optimal cut-off value of 95.5 U/L and an AUC of 0.745 (95% CI: 0.652-0.838). The survival analysis showed that high preoperative serum levels of AFP (≥250.0 ng/mL) and ALP (≥95.5 U/L) were significantly associated with the poor prognosis of HCC patients (P < 0.001). Based on the AFP-ALP score, all HCC patients were further divided into 0-point group (AFP < 250.0 ng/mL and ALP < 95.5 U/L), 1-point group (AFP≥250.0 ng/mL, ALP < 95.5 U/L; or AFP < 250.0 ng/mL, ALP ≥95.5 U/L), and 2-point group (AFP≥250.0 ng/mL and ALP≥95.5 U/L). The survival curves showed that the 0-, 1-, and 2-point groups had a median DFS of 60.0 (56.7-67.3) months, 20.0 (1.4-36.6) months, and 13.0(7.9-18.0) months, respectively, and there were significant survival differences between the three groups (P < 0.05). Serum AFP-ALP score (1 point vs 0 point: hazard ratio [HR]=4.060, 95% confidence interval [CI]: 2.050-8.039, P < 0.001; 2 points vs 0 point: HR=4.583, 95%CI: 2.385-8.805, P < 0.001) was an independent prognostic factor for HCC patients. Conclusion The scoring system based on the serum levels of AFP and ALP can effectively identify HCC patients with poor prognosis, and therefore, it might be used as a simple and reliable tool for prognostic assessment in the clinical treatment of HCC.
- Carcinoma, Hepatocellular /
- alpha-Fetoproteins /
- Alkaline Phosphatase /
- Prognosis

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图 1 血清AFP、ALP预测HCC患者预后的ROC曲线与生存曲线

Figure 1. ROC curves and Kaplan-Meier curves of HCC patients for survival prediction based on serum AFP and ALP levels

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图 2 血清AFP联合ALP评分与HCC患者预后关系的生存曲线

Figure 2. Kaplan-Meier curves of survival outcome in HCC patients based on the serum AFP and ALP levels

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表 1 AFP联合ALP不同评分的基线特征比较

Table 1. Comparison of baseline characteristics between different groups based on the serum AFP and ALP levels

临床变量	0分(n=32)	1分(n=63)	2分(n=59)	χ²值	P值
年龄[例(%)]				2.088	0.352
＜60岁	17 (53.1)	33 (52.4)	24 (40.7)
≥60岁	15 (46.9)	30 (47.6)	35 (59.3)
性别[例(%)]				1.463	0.481
女	9 (28.1)	25 (39.7)	19 (32.2)
男	23 (71.9)	38 (60.3)	40 (67.8)
HBV感染[例(%)]				4.971	0.083
无	12 (37.5)	14 (22.2)	10 (16.9)
有	20 (62.5)	49 (77.8)	49 (83.1)
肝硬化[例(%)]				0.069	0.966
无	7 (21.9)	14 (22.2)	12 (20.3)
有	25 (78.1)	49 (77.8)	47 (79.7)
肿瘤个数[例(%)]				6.116	0.047
单发	29 (90.6)	49 (77.8)	40 (67.8)
多发	3 (9.4)	14 (22.2)	19 (32.2)
肿瘤直径[例(%)]				2.724	0.256
≤5 cm	15 (46.9)	35 (55.6)	24 (40.7)
＞5 cm	17 (53.1)	28 (44.4)	35 (59.3)
肝包膜[例(%)]				1.577	0.454
无	22 (68.8)	36 (57.1)	33 (55.9)
有	10 (31.2)	27 (42.9)	26 (44.1)
TNM分期[例(%)]				4.802	0.091
Ⅰ~Ⅱ	11 (34.4)	12 (19.0)	9 (15.3)
Ⅲ	21 (65.6)	51 (81.0)	50 (84.7)
BCLC分期[例(%)]				11.279	0.024
A	9 (28.1)	7 (11.1)	7 (11.9)
B	17 (53.1)	33 (52.4)	23 (39.0)
C	6 (18.8)	23 (36.5)	29 (49.2)
微血管侵犯[例(%)]				11.631	0.003
否	21 (65.6)	44 (69.8)	24 (40.7)
是	11 (34.4)	19 (30.2)	35 (59.3)

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表 2 HCC患者预后因素的单因素及多因素Cox回归分析

Table 2. Univariate and multivariate Cox regression analysis of prognostic factors for HCC patients

临床变量	单因素分析		多因素分析
临床变量	HR(95%CI)	P值	HR(95%CI)	P值
年龄(≥60岁vs＜60岁)	1.027 (0.710~1.485)	0.888
性别(男vs女)	1.175 (0.796~1.736)	0.416
HBV感染(有vs无)	1.206 (0.777~1.871)	0.403
肝硬化(有vs无)	1.119 (0.714~1.753)	0.624
肿瘤个数(多发vs单发)	1.313 (0.854~2.018)	0.215
肿瘤直径(＞5 cm vs ≤5 cm)	1.719 (1.181~2.502)	0.005	1.681 (1.138~2.484)	0.009
肝包膜(有vs无)	1.263 (0.868~1.836)	0.222
TNM分期(Ⅲ vs Ⅰ~Ⅱ)	3.322 (1.821~6.060)	＜0.001	1.811 (0.953~3.442)	0.066
BCLC分期(C vs A~B)	2.500 (1.719~3.636)	＜0.001	2.037 (1.379~3.010)	＜0.001
微血管侵犯(是vs否)	2.110 (1.456~3.057)	＜0.001	2.142 (1.442~3.182)	＜0.001
AFP联合ALP评分
1分vs 0分	3.029 (1.567~5.853)	0.001	4.060 (2.050~8.039)	＜0.001
2分vs 0分	4.813 (2.541~9.117)	＜0.001	4.583 (2.385~8.805)	＜0.001

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