The Research Of Serum Granzyme B Predicting The Efficacy Of Targeted Drugs Combined With PD-1 Inhibitor For Advanced Hepatocellular Carcinoma

Objective: To explore the value of serum granzyme B in predicting the efficacy of targeted drugs combined with PD-1 inhibitors in the treatment of advanced hepatocellular carcinoma.Methods:(1)A total of 50 patients with advanced hepatocellular carcinoma admitted to the Hepatobiliary Pancreatic and Splenic Surgery Department of Guangxi Zhuang Autonomous Region People’s Hospital from December 1,2020 to December 3,2022 were included in the study.After screening for inclusion and exclusion criteria,a total of 37 cases met the inclusion criteria,including 33 male patients and 4 female patients,The observation endpoint is 9-12 weeks after the first targeted drug combined with PD-1 inhibitor treatment(equivalent to between the third and fourth treatment courses).According to the modified response evaluation criteria in solid tumors(m RECIST),the short-term early efficacy of the targeted drug combined with PD-1 inhibitor in mid to late stage hepatocellular carcinoma is determined.The serum of patients before medication was extracted,and the serum granzyme B concentration of each case was measured by Elisa test method;(2)The level of serum granzyme B in the peripheral blood of patients with advanced hepatocellular carcinoma before treatment,the clinical characteristics of patients and the efficacy were analyzed by single factor analysis and multi factor correlation analysis;(3)The receiver operating characteristic curve(ROC)curve was used to analyze the value of serum granzyme B before administration in predicting the efficacy of targeted drugs combined with PD-1 inhibitors for advanced hepatocellular carcinoma.Result:(1)A total of 37 patients were included in this study.After the first targeted drug combined with PD-1 inhibitor treatment for 9-12 weeks(equivalent to between the third and fourth treatment courses),the target tumor treatment effect was determined: 17 patients had disease control and 20 patients had disease progression;The total disease control rate(DCR)is45.95%.The analysis showed that the serum granzyme B concentration of patients before medication was correlated with the treatment effect.The results showed that the higher the serum granzyme concentration of patients before medication,the greater the possibility of remission of patients with advanced liver cancer receiving targeted drugs combined with PD-1inhibitors(P<0.05).The optimal cut-off value of serum granzyme B concentration of patients before administration was 0.110pg/ml calculated by ROC curve.At this point,the area under the curve is 0.707,and the sensitivity and specificity of predicting efficacy can reach 88.9%and 78.9%,respectively;(2)Single factor analysis showed that vascular invasion and alpha fetoprotein were the negative influencing factors of serum granzyme B concentration before treatment(P<0.05);(3)The general clinical data of patients and the single factor analysis of the serum granzyme B concentration before administration suggest that the combination of interventional therapy,vascular invasion,the serum granzyme B concentration before administration,and alpha fetoprotein are the factors influencing the therapeutic effect of targeted drugs combined with PD-1 inhibitors for advanced hepatocellular carcinoma,Incorporating meaningful variables from univariate analysis into binary logistic regression analysis suggests that vascular invasion is an independent risk factor for the efficacy of targeted drugs combined with PD-1 inhibitors in the treatment of advanced hepatocellular carcinoma;The concentration of serum granzyme B before administration was an independent protective factor for the efficacy of targeted drugs combined with PD-1 inhibitors in the treatment of advanced hepatocellular carcinoma(P<0.05).Conclusion:(1)In this study,it was found that the disease control rate of targeted drugs combined with PD-1 inhibitors in the treatment of advanced hepatocellular carcinoma was45.95%.The pre medication serum granzyme B concentration had a certain predictive value for the therapeutic effect of targeted drugs combined with PD-1 inhibitors in the treatment of advanced hepatocellular carcinoma.When the pre medication serum granzyme B concentration was greater than 0.110pg/ml,the prognosis of patients might be better;(2)In this study,it was found that vascular invasion is an independent risk factor for the efficacy of targeted drugs combined with PD-1 inhibitors in the treatment of mid and advanced hepatocellular carcinoma,and serum granzyme B concentration before treatment is an independent protective factor for the efficacy of targeted drugs combined with PD-1 inhibitors in the treatment of mid and advanced hepatocellular carcinoma.