血管性血友病因子/解整合素金属蛋白酶 13 比值作为肝细胞癌早期检测的潜在生物标志物。
VWF/ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma.
机构信息
Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara, 634-8522, Japan.
Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan.
出版信息
BMC Gastroenterol. 2019 Oct 21;19(1):167. doi: 10.1186/s12876-019-1082-1.
BACKGROUND
To investigate the von Willebrand factor to ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma (HCC) in cirrhosis.
METHODS
Serum levels of alpha-fetoprotein, des-γ-carboxy prothrombin, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (alpha-fetoprotein-L3%), vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, as well as the plasma levels of von Willebrand factor antigen (von Willebrand factor: Ag) and ADAMTS13 activity (ADAMTS13:AC), were evaluated in 41 cirrhotic patients with HCC undergoing radiofrequency ablation and in 20 cirrhotic patients without HCC. The diagnostic accuracy of each biomarker was evaluated using the receiver operating characteristic curve analysis.
RESULTS
The von Willebrand factor: Ag and von Willebrand factor: Ag/ADAMTS13:AC ratios were significantly higher in cirrhotic patients with HCC than in those without HCC (p < 0.05 and p < 0.01, respectively), whereas ADAMTS13:AC was significantly lower in those with HCC than those without HCC (p < 0.05). However, no relationship was observed between the von Willebrand factor: Ag/ADAMTS13:AC ratio and serum tumor markers such as alpha-fetoprotein, des-γ-carboxy prothrombin, and alpha-fetoprotein-L3%. Multivariate regression analysis identified von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% as significant factors of HCC development. Receiver operating characteristic analysis showed that the von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% had a better performance than alpha-fetoprotein, des-γ-carboxy prothrombin, alpha-fetoprotein-L3%, vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, von Willebrand factor: Ag, and ADAMTS13:AC. The von Willebrand factor: Ag/ADAMTS13:AC ratio was exclusively correlated with tumor volume and stage as well as serum vascular endothelial growth factor levels.
CONCLUSIONS
The von Willebrand factor: Ag/ADAMTS13:AC ratio can potentially serve as a novel biomarker for early diagnosis of HCC in cirrhotic patients.
背景
探讨血管性血友病因子（von Willebrand factor，vWF）与解整合素金属蛋白酶 13（ADAMTS13）的比值（vWF:Ag/ADAMTS13:AC）作为肝硬化患者肝细胞癌（hepatocellular carcinoma，HCC）早期检测的潜在生物标志物。
方法
评估 41 例接受射频消融治疗的肝硬化合并 HCC 患者和 20 例肝硬化不合并 HCC 患者的血清甲胎蛋白（alpha-fetoprotein，AFP）、脱γ-羧基凝血酶原（des-γ-carboxy prothrombin，DCP）、扁豆凝集素结合型 AFP （Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein，AFP-L3%）、血管内皮生长因子（vascular endothelial growth factor，VEGF）和血管内皮生长因子受体-2（vascular endothelial growth factor receptor-2，VEGFR-2）水平，以及血浆 vWF 抗原（von Willebrand factor antigen，vWF:Ag）和 ADAMTS13 活性（ADAMTS13:AC）水平。采用受试者工作特征曲线（receiver operating characteristic curve，ROC）分析评估各生物标志物的诊断准确性。
结果
与不合并 HCC 的肝硬化患者相比，合并 HCC 的肝硬化患者的 vWF:Ag 和 vWF:Ag/ADAMTS13:AC 比值显著升高（均 P<0.05），而 ADAMTS13:AC 显著降低（P<0.05）。然而，vWF:Ag/ADAMTS13:AC 比值与 AFP、DCP 和 AFP-L3%等血清肿瘤标志物之间无相关性。多因素回归分析显示，vWF:Ag/ADAMTS13:AC 比值和 AFP-L3%是 HCC 发生的显著因素。ROC 分析显示，vWF:Ag/ADAMTS13:AC 比值和 AFP-L3%在诊断 HCC 方面优于 AFP、DCP、AFP-L3%、VEGF 和 VEGFR-2、vWF:Ag 和 ADAMTS13:AC。vWF:Ag/ADAMTS13:AC 比值仅与肿瘤体积和分期以及血清 VEGF 水平相关。
结论
vWF:Ag/ADAMTS13:AC 比值可能成为肝硬化患者 HCC 早期诊断的新型生物标志物。
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