Takaya H, Namisaki T, Shimozato N, Kaji K, Kitade M, Moriya K, Sato S, Kawaratani H, Akahane T, Matsumoto M, Yoshiji H. ADAMTS13 and von Willebrand factor are useful biomarkers for sorafenib treatment efficiency in patients with hepatocellular carcinoma. World J Gastrointest Oncol 2019; 11(5): 424-435 [PMID: 31139312 DOI: 10.4251/wjgo.v11.i5.424]
Corresponding Author of This Article
Hiroaki Takaya, MD, PhD, Assistant Professor, Third Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan. htky@naramed-u.ac.jp
Research Domain of This Article
Oncology
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Hiroaki Takaya, Tadashi Namisaki, Naotaka Shimozato, Kosuke Kaji, Mitsuteru Kitade, Kei Moriya, Shinya Sato, Hideto Kawaratani, Takemi Akahane, Hitoshi Yoshiji, Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan
Masanori Matsumoto, Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan
Author contributions: Takaya H, Shimozato N, Kaji K, Kitade M, Moriya K, Sato S, Kawaratani H, Akahane T and Matsumoto M performed data analysis; Takaya H, Namisaki T and Yoshiji H contributed to the writing of the manuscript.
Institutional review board statement: Informed consent for the use of resected tissue was obtained from all patients and the study protocol was approved by the Ethics Committee of Nara Medical University.
Informed consent statement: All study participants or their legal guardians provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Hiroaki Takaya, MD, PhD, Assistant Professor, Third Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan. htky@naramed-u.ac.jp
Telephone: +81-744-223051 Fax: +81-744-247122
Received: January 30, 2019 Peer-review started: February 14, 2019 First decision: March 14, 2019 Revised: March 26, 2019 Accepted: April 8, 2019 Article in press: April 8, 2019 Published online: May 15, 2019 Processing time: 106 Days and 4.8 Hours
ARTICLE HIGHLIGHTS
Research background
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.
Research motivation
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.
Research objectives
To investigate ADAMTS13 and VWF as potential biomarkers for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.
Research 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 and multivariate analyses were used to determine predictive factors for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.
Research results
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).
Research conclusions
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.
Research perspectives
This is the first report the ADAMTS13-VWF imbalance in association with sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.
