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维生素K缺乏或拮抗剂-II诱导的血清蛋白、甲胎蛋白和剪接型乙型肝炎病毒联合检测在乙型肝炎病毒诱导的肝细胞癌中的诊断和预后价值

Diagnostic and Prognostic Value of Combined Detection of Serum Protein Induced by Vitamin K Absence or Antagonist-II, Alpha-Fetoprotein, and Spliced Hepatitis B Virus in Hepatitis B Virus-Induced Hepatocellular Carcinoma.

作者信息

Guo Zhentian, Mo Haixing, Yuan Yuqing, Fu Wenjin

机构信息

Department of Infectious Diseases, The First Clinical School of Guangdong Medical University, Zhanjiang, China.

Department of Laboratory Medicine, The Tenth Affiliated Hospital of Southern Medical University(Dongguan People's Hospital), Dongguan, China.

出版信息

Cancer Biother Radiopharm. 2025 Jul 2. doi: 10.1089/cbr.2025.0085.

DOI:10.1089/cbr.2025.0085
PMID:40600824
Abstract

To demonstrate the diagnostic and prognostic value of combined detection of serum abnormal prothrombin II (PIVKA II), α-fetoprotein (AFP), and spliced variants of hepatitis B virus genomes (spHBV) in HBV-induced hepatocellular carcinoma (HCC). From March 2018 to May 2019, samples were collected from 125 patients with HBV-related hepatocellular carcinoma (HBV-HCC), 125 patients with pure HBV (HBV group), and 125 patients with HBV-induced cirrhosis (HBV cirrhosis group), all of whom were receiving treatment at the hospital. Serum levels of PIVKA-II, AFP, and spHBV were measured using an immunochemiluminescence detection system, a fully automated immunoassay analyzer, and a real-time quantitative polymerase chain reaction instrument, respectively. Kaplan-Meier method was applied to analyze relationship among serum PIVKA-II, AFP, spHBV, and prognosis of patients with HBV-HCC; cyclooxygenase (COX) risk regression analyzed factors affecting prognosis of patients with HBV-HCC; receiver operating characteristic (ROC) curve evaluated diagnostic and prognostic predictive efficacy of serum PIVKA-II, AFP, and spHBV alone or combined for HBV-HCC. The serum concentrations of PIVKA-II, AFP, and spHBV in the HBV-HCC group were significantly higher than those in the HBV cirrhosis group and the HBV group (all < 0.05). The HBV cirrhosis group also showed significantly higher levels compared with the HBV group ( < 0.05). Serum PIVKA-II, AFP, spHBV, tumor number, tumor-node-metastasis (TNM) stage, and extrahepatic metastasis differed markedly between dead patients and surviving patients ( < 0.05). PIVKA-II, AFP, and spHBV in patients with HBV-HCC were related to tumor number, TNM staging, and extrahepatic metastasis ( < 0.05).The 36-month survival rate of patients with high-expression PIVKA-II was inferior to patients with low expression ( = 6.561, = 0.010); the 36-month survival rate of patients with high-expression AFP was inferior to patients with low expression ( = 4.789, = 0.029); and the 36-month survival rate of patients with high-expression spHBV was inferior to patients with low expression ( = 5.761, = 0.016). Multivariate logistic regression analysis showed that high expression of PIVKA-II, AFP, spHBV in serum, multiple tumors, TNM staging of stage III-IV, and extrahepatic metastasis were all risk factors for death in patients with HBV-HCC ( < 0.05). The area under the curve (AUC) of the combination of serum PIVKA-II, AFP, and spHBV in the diagnosis for HBV-HCC was markedly higher than PIVKA-II, AFP, and spHBV alone diagnosis ( < 0.05). The AUC predicted by the combination of serum PIVKA-II, AFP, and spHBV in predicting the prognosis of patients with HBV-HCC was markedly higher than that predicted by the three factors alone ( < 0.05). Serum PIVKA-II, AFP, and spHBV joint detection has significant clinical value for diagnosis and prognosis of HBV-HCC.

摘要

探讨血清异常凝血酶原II(PIVKA II)、甲胎蛋白(AFP)及乙型肝炎病毒基因组剪接变异体(spHBV)联合检测在乙型肝炎病毒(HBV)所致肝细胞癌(HCC)中的诊断及预后价值。2018年3月至2019年5月,收集在本院接受治疗的125例HBV相关肝细胞癌(HBV-HCC)患者、125例单纯HBV感染患者(HBV组)及125例HBV所致肝硬化患者(HBV肝硬化组)的样本。分别采用免疫化学发光检测系统、全自动免疫分析分析仪及实时定量聚合酶链反应仪检测血清PIVKA-II、AFP及spHBV水平。应用Kaplan-Meier法分析血清PIVKA-II、AFP、spHBV与HBV-HCC患者预后的关系;采用环氧化酶(COX)风险回归分析影响HBV-HCC患者预后的因素;绘制受试者工作特征(ROC)曲线评估血清PIVKA-II、AFP及spHBV单独或联合检测对HBV-HCC的诊断及预后预测效能。HBV-HCC组血清PIVKA-II、AFP及spHBV浓度显著高于HBV肝硬化组及HBV组(均P<0.05)。HBV肝硬化组水平也显著高于HBV组(P<0.05)。死亡患者与存活患者的血清PIVKA-II、AFP、spHBV、肿瘤数目、肿瘤-淋巴结-转移(TNM)分期及肝外转移情况差异有统计学意义(P<0.05)。HBV-HCC患者的PIVKA-II、AFP及spHBV与肿瘤数目、TNM分期及肝外转移相关(P<0.05)。PIVKA-II高表达患者的36个月生存率低于低表达患者(χ²=6.561,P=0.010);AFP高表达患者的36个月生存率低于低表达患者(χ²=4.789,P=0.029);spHBV高表达患者的36个月生存率低于低表达患者(χ²=5.761,P=0.016)。多因素logistic回归分析显示,血清PIVKA-II、AFP、spHBV高表达、多发肿瘤、TNM分期为III-IV期及肝外转移均为HBV-HCC患者死亡的危险因素(P<0.05)。血清PIVKA-II、AFP及spHBV联合检测诊断HBV-HCC的曲线下面积(AUC)显著高于单独检测PIVKA-II、AFP及spHBV(P<0.05)。血清PIVKA-II、AFP及spHBV联合检测预测HBV-HCC患者预后的AUC显著高于三者单独检测预测值(P<0.05)。血清PIVKA-II、AFP及spHBV联合检测对HBV-HCC的诊断及预后评估具有重要临床价值。

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