Abstract:

Objective To study the roles of zinc finger BED domain-containing protein 3（ZBED3），cytokeratin 19 fragment antigen 21-1（CYFRA21-1），vascular endothelial growth factor（VEGF） in risk assessment of advanced liver cancer patients.Methods A retrospective analysis was conducted on 99 patients with advanced liver cancer treated in Liangping District People's Hospital from January 2020 to December 2022. The clinical data were collected，and ZBED3，CYFRA21-1，VEGF，alpha-fetoprotein（AFP），protein induced by vitamin K absence or antagonist-Ⅱ（PIVKAⅡ） and white blood cell（WBC） count were determined. Neutrophil/lymphocyte ratio（NLR） was calculated. All the patients were followed up for 180 d and classified into death group（35 cases） and survival group（64 cases）. Spearman correlation analysis was used to evaluate the correlation among the indicators. Receiver operating characteristic（ROC） curve was used to evaluate the efficacy of each indicator in determining short-term mortality in patients with advanced liver cancer. Kaplan-Meier survival curve was used to analyze the survival of patients with advanced liver cancer. Cox regression analysis was used to evaluate the influencing factors of mortality in patients with advanced liver cancer.Results CYFRA21-1，VEGF，ZBED3，AFP，PIVKAⅡ，WBC count，NLR and Child-Pugh score in death group were higher than those in survival group（P<0.001），and there was no statistical significance in the other indicators between the 2 groups（P>0.05）. There were positive correlations between CYFRA21-1，VEGF，ZBED3，Child-Pugh score，AFP，PIVKAⅡ，WBC count and NLR（r values were 0.609，0.364，0.760，0.759，0.651，0.639，0.527 and 0.728，respectively，P<0.05）. The areas under curves（AUC） of CYFRA21-1，ZBED3，Child-Pugh score，VEGF，AFP，PIVKAⅡ，WBC count and NLR were 0.868，0.720，0.959，0.955，0.893，0.886，0.818 and 0.939，respectively. The survival rate of high-level CYFRA21-1，VEGF and ZBED3 groups（26.5%，15.0% and 3.3%） were lower than those of low-level groups（84.5%，77.2% and 91.3%）（Log-rank χ²=37.424，32.449 and 99.247，P<0.001）. AFP，WBC count，ZBED3 and Child-Pugh score were all risk factors for short-term mortality in advanced liver cancer patients [hazard ratios（HR） were 1.008，1.946，1.013 and 1.237，95% confidence intervals（CI）were 1.002-1.014，1.418-2.672，1.028-1.042 and 1.049-1.460，P<0.05].Conclusions ZBED3，CYFRA21-1 and VEGF are associated with mortality risk in patients with advanced liver cancer，and the combined determination of ZBED3，AFP，WBC count and Child-Pugh score has a high predictive value for the short-term mortality risk in patients with advanced liver cancer.

Key words: Zinc finger BED domain-containing protein 3, Cytokeratin 19 fragment antigen 21-1, Vascular endothelial growth factor, Liver cancer, Mortality risk