Correlation Between SPD-1 In Peripheral Blood Of Patients With Hepatocellular Carcinoma And Detection Of PD-1 In Hepatocellular Carcinoma Specimens And Its Relationship With Prognosis

Objective:To detect the expression of soluble programmed death 1（sPD-1）in peripheral blood and programmed death 1（PD-1）in liver tissues of patients with hepatocellular carcinoma（HCC）,and then to analyse the correlation between sPD-1 and PD-1 expression and its relationship with prognosis of HCC.Methods:1.We select 49 patients who were diagnosed as primary liver cancer by s ome examinations,such as,CT/MRI,PET-CT,contrast-enhanced ultrasound（CEUS）or puncture biopsy from November 2019 to December 2020 in Chifeng Clinical Medical College of Inner Mongolia Medical University.Immunohistochemical method and enzy me-linked immunosorbent assay（ELISA）were used to detect the expression of PD-1 i n HCC cancer tissues and peripheral blood of 49 patients with HCC after hepatectomy.And use statistical methods to analyse the correlation between the expression of PD-1and the concentration of sPD-1,and the relationship between the expression of PD-1and the concentration of sPD-1 and the clinicopathological features.2.Relevant liter atures were searched,and a meta-analysis was conducted to estimate the relationship with overall survival of HCC patients.Results:1.The results of PD-1 immunohistochemical staining of liver cancer tissue samples showed that the expression of PD-1 was detected in 45 of the 49 cases,and the positive rate was 91.8%.In the positive expression group of PD-1,22 cases were weakly positive（+）and23 cases were moderately positive（++）of PD-1.2.The results of ELISA in peripheral blood of patients with HCC showed that the concentration of sPD-1 in peripheral blood of patients with liver cancer was in the range of 521.76-3432.06pg/ml,and the average concentration was 1508.81pg/ml.The correlation analysis of the expression level of PD-1、sPD-1 in peripheral blood and liver cancer tissue samples showed that the concentration of sPD-1 in the negative group of PD-1 expression was significantly higher than that in the positive group（P=0.006）.The level of sPD-1 expression in the moderate positive group of PD-1 expression was significantly lower than that in the weakly positive group of PD-1expression,and there was significant difference between the moderate positive group and the weakly positive group of PD-1 expression（P=0.019）.Through Speamran correlation analysis,there was no correlation between the expression of PD-1 in pathological tissue and the concentration of sPD-1 in peripheral blood（r_s=﹣0.242,P=0.093）.However,there was a negative correlation between the expression of PD-1（negative,weakly positive and moderately positive）and the concentration of sPD-1 in peripheral blood（r_s=﹣0.462,P=0.001）,and there was a negative correlation between the concentration of sPD-1 in peripheral blood and the positive expression of PD-1 in pathological tissue（r_s=﹣0.431,P=0.003）.3.The analysis of the relationship between the expression level of PD-1 in peripheral blood sPD-1 and tissue samples of HCC patients and the clinicopathological characteristics of HCC patients showed that among the 45 HCC patients with PD-1 positive expression,the number of moderately differentiated patients was the highest in the weakly positive group and the moderately positive group was the highest,and the difference was statistically significant（P=0.000）.Through Speamran correlation analysis,there was a negative correlation between the positive expression of PD-1 and pathological grade（r_s=﹣0.538,P=0.000）.In 49 patients with different pathological grades,the expression level of sPD-1 in poorly differentiated patients was significantly lower than that in moderately differentiated and well differentiated patients(P _low-medium=0.011,P _low-high=0.003),and the expression level of sPD-1 in moderately differentiated patients was slightly lower than that in well differentiated patients,but the difference was not statistically significant（P medium-high=1.000）.Through Speamran correlation analysis,there was a positive correlation between sPD-1 concentration in peripheral blood and pathological grade（r_s=0.511,P=0.000）.Other clinical and pathological features such as clinical stage,liver function grade,tumor size,AFP expression level and vascular invasion were not found to be significantly different and correlated with the concentration of sPD-1 in peripheral blood and the expression of PD-1 in pathological tissues of patients with HCC.4.Meta analysis showed that there were significant differences（Z=2.12,P<0.05）in OS between PD-1 high expression group and PD-1 low expression group.（Hr=1.30;95%CI:1.02～1.65）.It means that the high expression of PD-1 indicates that the overall survival rate of patients with liver cancer is poor,and the prognosis is even worse.There was no significant difference in OS between the high sPD-1 concentration group and the low sPD-1 concentration group（Hr=0.95;95%CI:0.32～2.97）,and there was no significant difference between the two groups（Z=0.09,P>0.05）.Conclusion:1.There was a negative correlation between the expression level of sPD-1 in peripheral blood of patients with liver cancer and the expression level of PD-1 in liver cancer tissue samples.2.There was a positive correlation between the expression level of sPD-1 in peripheral blood and pathological grade of patients with liver cancer,while there was a negative correlation between the positive expression of PD-1 in liver cancer tissue and pathological grade.Other clinical and pathological features such as clinical stage,liver function grade,tumor size,AFP expression level and vascular invasion were not correlated with the expression level of sPD-1 in peripheral blood and PD-1 in liver cancer tissue specimens.3.Meta analysis showed that the high expression of PD-1 predicted a poor overall survival rate and a worse prognosis in patients with liver cancer.