ADAMTS13 and von Willebrand factor are useful biomarkers for sorafenib treatment efficiency in patients with hepatocellular carcinoma

作     者：Hiroaki Takaya Tadashi Namisaki Naotaka Shimozato Kosuke Kaji Mitsuteru Kitade Kei Moriya Shinya Sato Hideto Kawaratani Takemi Akahane Masanori Matsumoto Hitoshi Yoshiji 

作者机构：Third Department of Internal Medicine Nara Medical University Department of Blood Transfusion Medicine Nara Medical University 

出 版 物：《World Journal of Gastrointestinal Oncology》 (世界胃肠肿瘤学杂志（英文版）（电子版）)

年 卷 期：2019年第11卷第5期

页      面：424-435页

核心收录：

学科分类：1002[医学-临床医学] 10[医学] 

主　　题：ADAMTS13 Von Willebrand factor Biomarkers Hepatocellular carcinoma Sorafenib 

摘      要：BACKGROUND Many advanced hepatocellular carcinoma(HCC) patients are receiving sorafenib treatment. Sorafenib reportedly improves overall survival(OS) significantly in patients with HCC. Prediction of sorafenib response and prognosis in patients with HCC receiving sorafenib treatment are important due to the potentially serious side effects of sorafenib. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) and von Willebrand factor(VWF) are associated with the pathophysiology of liver cirrhosis and HCC through their roles in hypercoagulability; they are also associated with angiogenesis via vascular endothelial growth factor(VEGF). The imbalance between ADAMTS13 and VWF was associated with prognosis of various cancers in patients undergoing chemotherapy.AIM To investigate ADAMTS13 and VWF as potential biomarkers for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.METHODS Forty-one patients with HCC receiving sorafenib treatment were included in this study. The initial daily sorafenib dose was 400 mg in all patients. ADAMTS13 activity(ADAMTS13:AC), VWF antigen(VWF:Ag), VEGF levels were determined by enzyme-linked immunosorbent assay. Univariate andmultivariate analyses were used to determine predictive factors for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.RESULTS ADAMTS13:AC was significantly higher in patients with stable disease(SD),partial response(PR), and complete response(CR) than in those with progressive disease(PD)(P 0.05). In contrast, VWF:Ag and the VWF:Ag/ADAMTS13:AC ratio were significantly lower in patients with SD, PR, and CR than in those with PD(P 0.05 for both). Multivariate analysis showed that the VWF:Ag/ADAMTS13:AC ratio was the only predictive factor for sorafenib response and ADAMTS13:AC was the only prognostic factor in patients with HCC receiving sorafenib treatment. The patients with a low ADAMTS13:AC(78.0) had significantly higher VEGF levels than those with a high ADAMTS13:AC(≥ 78.0)(P 0.05).CONCLUSION The VWF:Ag/ADAMTS13:AC ratio and ADAMTS13:AC are potentially useful biomarkers for sorafenib response and prognosis, respectively, in patients with HCC receiving sorafenib treatment.