| Objectives: To observe the expression levels of soluble programmed cell death ligand-1(sPD-L1)and vascular endothelial growth factor(VEGF)in peripheral blood of healthy people and patients with hepatocellular carcinoma(HCC)treated with immunotherapy combined with anti-angiogenic drugs before and after treatment,so as to explore the differences in their expression in the peripheral blood of healthy people and HCC patients,and also to explore their value for the efficacy and prognostic assessment of immunotherapy combined with anti-angiogenic drugs in the treatment of hepatocellular carcinoma.Methods:(1)Patients with hepatocellular carcinoma of middle-later period who were hospitalized at the Affiliated Hospital of Guilin Medical College from November 2021 to November 2022 and were treated with PD-1 inhibitors in combination with anti-angiogenic drugs for the first time were selected.Healthy people were also selected as the control group.Clinical data were collected from the included patients and the patients were evaluated for efficacy based on their imaging data after at least 2 cycles of treatment and followed up for progression-free survival.(2)Serum samples were collected from HCC patients before and after 2 cycles of treatment,and from the enrolled healthy people,and serum samples were stored in a refrigerator at-80℃.The concentrations of sPD-L1 and VEGF in serum samples were measured by enzyme linked immunosorbent assay(ELISA)in batches.(3)Measures conforming to a normal distribution are expressed as mean ± standard deviation,and those not normally distributed are expressed as median(interquartile range).Count data are expressed as number of cases(n)and rate(%).Two groups were compared by t-test or rank sum test,and rates were compared by chi-square test or Fisher’s exact test.The Kaplan-Meier method was used to plot survival curves,and the Log-rank test was used to compare the differences in progression-free survival,and the Cox regression model was used to analyze the factors influencing prognosis.P < 0.05 was considered a statistically significant difference.Results: A total of 38 healthy people and 40 patients with HCC were enrolled in this study.The age range of the enrolled HCC patients was 24-82 years,with a median age of 59 years.Recent efficacy evaluation: 0 cases of complete remission,9 cases of partial remission,27 cases of stable disease,and4 cases of disease progression,with an objective response rate(ORR)of 22.5%and a disease control rate(DCR)of 90.0%.Long-term efficacy evaluation:median progression-free survival(PFS)was 4.8 months.The expression levels of peripheral blood sPD-L1 and VEGF were higher in HCC patients than in the healthy people(P < 0.001;P < 0.001).The sPD-L1 expression level correlated with vascular invasion and hepatitis B virus(HBV)DNA load(P = 0.006;P =0.018).The differences in the expression levels of peripheral blood sPD-L1 and VEGF in HCC patients before and after treatment were not statistically significant(P > 0.05).The ORR and DCR of different sPD-L1 and VEGF expression levels were not statistically different(P > 0.05).There was no statistical difference in sPD-L1 and VEGF expression levels before and after treatment among patients with different efficacy evaluation results(P > 0.05).The results of Cox regression analysis showed that VEGF,the longest diameter of measurable lesions and distant metastases were independent risk factors for the PFS of HCC patients(P > 0.05).Conclusions:(1)Peripheral blood sPD-L1 and VEGF levels may not predict the efficacy of PD-1 inhibitors in combination with anti-vascular drugs for the treatment of HCC.(2)HCC patients with high peripheral blood VEGF levels,high tumor load or distant metastases may have a poor prognosis.(3)sPD-L1 expression levels in peripheral blood correlate with vascular invasion and HBV DNA load.(4)sPD-L1 and VEGF may be potential biomarkers to aid in the diagnosis of HCC. |
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