Association between ADAMTS13 activity-VWF antigen imbalance and the therapeutic effect of HAIC in patients with hepatocellular carcinoma

World J Gastroenterol. 2020 Dec 7;26(45):7232-7241. doi: 10.3748/wjg.v26.i45.7232.

Abstract

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.

Keywords: ADAMTS13; Biomarkers; HAIC; Hepatocellular carcinoma; Vascular endothelial growth factor; Von Willebrand factor.

MeSH terms

  • ADAMTS13 Protein
  • Carcinoma, Hepatocellular* / drug therapy
  • Humans
  • Liver Neoplasms* / drug therapy
  • Prognosis
  • Vascular Endothelial Growth Factor A
  • von Willebrand Factor

Substances

  • Vascular Endothelial Growth Factor A
  • von Willebrand Factor
  • ADAMTS13 Protein
  • ADAMTS13 protein, human