Correlation Between Peripheral Blood DCK Expression And Immunity In Patients With Hepatocellular Carcinoma

Objective: The purpose of this study was to investigate the expression level of immune-related gene deoxycytidine kinase(DCK)in peripheral blood of patients with hepatocellular carcinoma(HCC)and its role in the tumor immune microenvironment,and to explore the correlation between DCK and clinical features and its value in predicting the efficacy of immunotherapy.Methods:(1)Preliminary exploration of the expression levels of DCK in peripheral blood of HCC patients and healthy people based on GEO database.Gene set enrichment analysis(GSEA)and CIBERSORT software were used to preliminarily explore the role of DCK in the immune microenvironment of HCC patients.TIDE algorithm was used to explore the value of DCK in predicting the efficacy of immunotherapy.(2)All newly diagnosed HCC patients treated with immune checkpoint inhibitor monotherapy or combination therapy in the Department of Oncology,Affiliated Hospital of Guilin Medical College from September 2021 to January 2022 were collected.The clinical characteristics of HCC patients were recorded,and the short-term efficacy was evaluated by imaging after immunotherapy.(3)Fasting blood was collected from all patients within 1 week before medication.The expression level of DCK in peripheral blood of HCC patients was verified by q RT-PCR,and its correlation with clinical characteristics as well as its value in predicting the efficacy of immunotherapy were explored.(4)Measurement data were expressed by mean± standard deviation and compared between groups by t-test.Count data were expressed by number of cases and rate(%),and chi-square test was used for comparison between groups.Spearman correlation test was used to analyze the correlation between target gene and immune cells.P<0.05 means the difference is statistically significant.R software(V4.1.1),SPSS 25.0,and Graphpad Prism8.0 were used for mapping and statistical analysis.Results:(1)By January 20,2022,a total of 25 patients with HCC were enrolled,8 of whom were excluded because they could not assess the curative effect,and finally 17 patients with HCC were enrolled.The minimum age was40 years,the maximum age was 68 years,and the median age was 58 years.Fifteen of the patients were male and 2 were female.All patients were in BCLC stage C.Five healthy volunteers served as the control group.Among the patients with evaluable efficacy,there were 0 cases of CR(0%),2 cases of PR(11.8%),9cases of SD(52.9%),and 6 cases of PD(35.3%).The disease control rate(DCR)was 64.7% and the objective remission rate(ORR)was 11.8%.(2)The results of GEO database showed that the expression level of DCK in peripheral blood of HCC patients was higher than that of healthy people.(3)The low expression group of DCK was mainly enriched in many immune-related biological functions such as macrophage activation,leukocyte migration,positive regulation of cytokine production,cell chemotaxis,etc.(4)The expression of DCK was negatively correlated with activated dendritic cells(P<0.001)and plasma cells(P<0.05)and tend to be negatively correlated with the content of many immune cells in peripheral blood.(5)The TIDE score of DCK high expression group was higher than that of DCK low expression group(P<0.05).(6)The expression of DCK was significantly correlated with tumor size and vascular invasion(P<0.05);the number of disease control was 50% in the high DCK group and 77.8% in the low DCK group;67% of the patients in the low DCK group showed a shrinking trend,and 63% of the patients in the high DCK group showed an increasing trend.Conclusions:(1)Bioinformatics analysis shows that DCK is highly expressed in the peripheral blood of HCC patients.(2)Bioinformatics analysis showed that the expression level of DCK in peripheral blood was negatively correlated with immune-related biological functions such as macrophage activation,leukocyte migration,positive regulation of cytokine production,cell chemotaxis,etc.DCK may play a negative regulatory role in the immune microenvironment of liver cancer through many immune-related biological functions such as those mentioned above.(3)Bioinformatics analysis showed that the expression level of DCK in peripheral blood was significantly negatively correlated with the content of DCs and plasma cells,and tend to be negatively correlated with the content of many immune cells in peripheral blood;DCK may play a key role in regulating immune cell infiltration and play an important role in immunosuppression and immune escape.(4)The higher the expression of DCK in peripheral blood,the worse the immunotherapy efficacy may be.(5)The high expression of DCK in peripheral blood may indicate poor clinical prognosis of HCC patients.