血清DKK1、TAP联合异常凝血酶原术前预测肝细胞癌微血管侵犯的价值

摘要/Abstract

摘要： 目的探究血清Dickkopf-1相关蛋白(DKK1)、肿瘤异常糖链蛋白(TAP)联合异常凝血酶原(PIVKA-Ⅱ)术前预测肝细胞癌(HCC)微血管侵犯(MVI)的价值。方法选择2021年9月至2024年8月启东市人民医院诊治的270例HCC患者作为HCC组,另选同期247例肝良性病变患者及283名体检志愿者作为良性组和对照组,根据是否发生MVI将HCC患者分为非MVI组(n=176)和MVI组(n=94)。检测乙型肝炎病毒(HBV)DNA定量、凝血酶原时间(PT)、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆红素(TBil)、甲胎蛋白(AFP)、DKK1、PIVKA-Ⅱ、TAP水平。多因素logistic回归分析评估MVI发生的影响因素;ROC曲线分析DKK1、TAP、PIVKA-Ⅱ对MVI发生的诊断价值,Z检验比较AUC的差异。结果 HCC组血清DKK1、TAP、PIVKA-Ⅱ水平[(147.95±45.36)pg/L、(184.90±58.72)μm²、(124.47±38.31)ng/mL]均高于良性组[(115.32±34.31)pg/L、(126.37±38.32)μm²、(75.28±24.74)ng/mL]、对照组[(96.45±28.44)pg/L、(86.21±25.34)μm²、(32.71±8.43)ng/mL]。与非MVI组相比,MVI组肿瘤直径≥5 cm、肿瘤数目多发、肿瘤低分化、HBV DNA定量> 10⁴ copies/mL、Child-Pugh分级B级占比及血清AFP、DKK1、TAP、PIVKA-Ⅱ水平较高(P<0.05)。肿瘤直径≥5 cm、肿瘤数目多发、肿瘤低分化及AFP、DKK1、TAP、PIVKA-Ⅱ水平升高是HCC患者发生MVI的独立危险因素(P<0.05);DKK1、TAP、PIVKA-Ⅱ单独诊断HCC患者发生MVI的AUC为0.773、0.788、0.777。三者联合诊断的AUC为0.934,优于各自单独诊断。结论 MVI患者血清DKK1、TAP、PIVKA-Ⅱ水平高于非MVI患者,三者均为MVI发生的独立危险因素,联合诊断MVI发生具有一定的临床意义,可为临床诊断提供参考。

关键词: 肝细胞癌, Dickkopf-1相关蛋白, 肿瘤异常糖链蛋白, 异常凝血酶原, 微血管侵犯, 诊断价值

Abstract: Objective To explore the value of serum Dickkopf-1 related protein (DKK1), tumor abnormal protein (TAP) combined with protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) in preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods A total of 270 HCC patients diagnosed and treated in Qidong People′s Hospital from September 2021 to August 2024 were regarded as the HCC group, and 247 patients with benign liver lesions and 283 physical examination volunteers were selected as the benign group and control group. HCC patients were assigned into non-MVI group (n=176) and MVI group (n=94) based on whether MVI occurred. Quantitative hepatitis B virus (HBV) DNA, prothrombin time (PT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBil), alpha-fetoprotein (AFP), DKK1, PIVKA-Ⅱ and TAP levels were determined. Multivariate logistic regression was applied to analyze the influencing factors of MVI occurrence. The ROC curve was applied to analyze the diagnostic value of DKK1, TAP, and PIVKA-II for the occurrence of MVI. The Z-test was applied to compare the difference in AUC. Results The levels of serum DKK1, TAP and PIVKA-Ⅱ in HCC group were (147.95±45.36) pg/L, (184.90±58.72) μm² and (124.47±38.31) ng/mL, respectively higher than the benign group [(115.32±34.31) pg/L, (126.37±38.32) μm², (75.28±24.74) ng/mL] and the control group [(96.45±28.44) pg/L, (86.21±25.34) μm², (32.71±8.43) ng/mL]. Compared with the non-MVI group, the MVI group had tumors with a diameter of ≥ 5 cm, multiple tumors, low tumor differentiation, HBV DNA quantification >10⁴ copies/mL, a higher proportion of Child Pugh grade B, and higher levels of serum AFP, DKK1, TAP, and PIVKA Ⅱ (P<0.05). Tumor diameter ≥ 5 cm, multiple tumors, low tumor differentiation, and elevated levels of AFP, DKK1, TAP, and PIVKA-Ⅱ were independent risk factors for MVI in HCC patients (P<0.05). The AUC values of DKK1, TAP, and PIVKA-Ⅱ for diagnosing MVI in HCC patients were 0.773, 0.788, and 0.777, respectively. The AUC of the combined diagnosis of the three was 0.934, which was better than the individual diagnosis. Conclusion The levels of serum DKK1, TAP, and PIVKA Ⅱ in patients with MVI are higher than those in non-MVI patients, and these three are independent risk factors for the occurrence of MVI. The combined diagnosis of MVI has certain clinical significance and provides reference for clinical diagnosis.

Key words: Hepatocellular carcinoma, Dickkopf-1 related protein, Tumor abnormal protein, Protein induced by vitamin K absence or antagonist-Ⅱ, Microvascular invasion, Diagnostic value

朱泓宇, 胡庆超, 宋庆杰, 宋辉, 朱忠辉. 血清DKK1、TAP联合异常凝血酶原术前预测肝细胞癌微血管侵犯的价值[J]. 肝脏, 2026, 31(3): 385-389.

ZHU Hong-yu, HU Qing-chao, SONG Qing-jie, SONG Hui, ZHU Zhong-hui. Application of serum DKK1, TAP combined with abnormal prothrombin in preoperative prediction of microvascular invasion in hepatocellular carcinoma[J]. Chinese Hepatolgy, 2026, 31(3): 385-389.

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