Copyright
©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Association between ADAMTS13 activity–VWF antigen imbalance and the therapeutic effect of HAIC in patients with hepatocellular carcinoma
Hiroaki Takaya, Tadashi Namisaki, Kei Moriya, Naotaka Shimozato, Kosuke Kaji, Hiroyuki Ogawa, Koji Ishida, Yuki Tsuji, Daisuke Kaya, Hirotestu Takagi, Yukihisa Fujinaga, Norihisa Nishimura, Yasuhiko Sawada, Hideto Kawaratani, Takemi Akahane, Masanori Matsumoto, Hitoshi Yoshiji
Hiroaki Takaya, Tadashi Namisaki, Kei Moriya, Naotaka Shimozato, Kosuke Kaji, Hiroyuki Ogawa, Koji Ishida, Yuki Tsuji, Daisuke Kaya, Yukihisa Fujinaga, Norihisa Nishimura, Yasuhiko Sawada, Hideto Kawaratani, Takemi Akahane, Hitoshi Yoshiji, Department of Gastroenterology, 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, Namisaki T, Moriya K, Shimozato N, Kaji K, Ogawa H, Ishida K, Tsuji Y, Kaya D, Takagi H, Fujinaga Y, Nishimura N, Sawada Y, Kawaratani H, and Akahane T performed data analysis; Takaya H, Namisaki T, Matsumoto M, and Yoshiji H wrote the manuscript.
Institutional review board statement: Informed consent for the use of resected tissue was obtained from all patients. 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.
Data sharing statement: Informed consent for data sharing was not obtained but the presented data are anonymized and the risk of identification is low.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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, Department of Gastroenterology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. htky@naramed-u.ac.jp
Received: August 4, 2020
Peer-review started: August 4, 2020
First decision: September 30, 2020
Revised: October 9, 2020
Accepted: November 13, 2020
Article in press: November 13, 2020
Published online: December 7, 2020
BACKGROUND
Prediction of HAIC treatment response is important for improving the prognosis in patients with hepatocellular carcinoma (HCC). The progression of HCC is related to hypercoagulability and angiogenesis. It is known that ADAMTS13 and von Willebrand factor (VWF) are related to hypercoagulability. In addition, previous study reported that the association between ADAMTS13 and VWF, and angiogenesis via vascular endothelial growth factor (VEGF). Recently, ADAMTS13 and VWF have been associated with the prognosis in patients with various kinds of cancer undergoing chemotherapy.
AIM
To investigate whether ADAMTS13 and VWF become useful biomarkers of treatment response in HCC patients before the initiation of HAIC treatment.
METHODS
Seventy-two patients were enrolled in this study. ADAMTS13 activity (ADAMTS13:AC), VWF antigen (VWF:Ag) and VEGF levels were determined via enzyme-linked immunosorbent assay. Univariable and multivariable analyses were performed to determine the predictive factors of treatment response in patients with HCC undergoing HAIC treatment.
RESULTS
ADAMTS13:AC levels in HCC patients with stable disease (SD) + partial response (PR) of HAIC treatment were significantly higher than those with progressive disease (PD) (P < 0.05). In contrast, VWF:Ag/ADAMTS13:AC ratio and VEGF levels in HCC patients with SD + PR were significantly lower than those with PD (both P < 0.05). Patients with high VWF:Ag/ADAMTS13:AC ratio (> 2.7) had higher VEGF levels than those with low ratio (≤ 2.7). Multivariable analysis revealed that VWF:Ag/ADAMTS13:AC ratio was a predictive factor of HAIC treatment response.
CONCLUSION
VWF:Ag/ADAMTS13:AC ratio may become a useful biomarker of treatment response in HCC patients before the initiation of HAIC treatment.
Core Tip: The prediction of HAIC treatment response is needed to improve the prognosis in patients with hepatocellular carcinoma (HCC). Von Willebrand factor antigen (VWF:Ag)/ADAMTS13 activity (ADAMTS13:AC) ratio was significantly lower in HCC patients with stable disease + partial response than those with progressive disease. VWF:Ag/ADAMTS13:AC ratio become a useful biomarker to predict HAIC treatment response.
