Expression And Significance Of Immune Checkpoint LAG-3 In Glioblastoma

Objective:To investigate the expression,potential function,prognosis and clinical significance of LAG-3 in glioblastoma.Methods:The basic information of LAG-3 was searched using NCBI,Uni Prot,and genecards databases;the expression information and expression differences of LAG-3 between GBM and normal brain tissue,as well as race,gender,and age were analyzed by searching GEPIA database,Oncomine database,and UALCAN database,and further survival analysis was performed;the expression validation of LAG-3 in GBM was performed by immunohistochemistry;15 genes co-expressed with LAG-3 were retrieved in Oncomine database,GO function and KEGG pathway enrichment analysis were performed on the gene set using Omicshare online software,and the potential main role relationship and function of this group of gene sets were predicted by Gene MANIA database.Finally,the relationship between LAG-3 expression and immune infiltration in GBM was analyzed by TIMER database.Results:GEPIA database and Oncomine database showed that the expression of LAG-3 in glioblastoma tissues was significantly higher than that in normal tissues(p < 0.05).The high expression of LAG-3 in GBM had no significant effect on the overall survival rate of GBM(P > 0.05).Except for yellow race,the expression level of LAG-3 in GBM tissues of white and black race was significantly higher than that in normal tissues.Although the differential expression of LAG-3 was not significant in Asian race,the difference in the results may be related to the small sample size of Asian race in the database.Also there was no significant difference in the expression of LAG-3 in GBM between male and female patients.The expression level of LAG-3 was significantly higher than that of normal brain tissue in the 21 – 80 age group,with no statistically significant difference over 80 years of age;GEPIA database analysis of prognosis suggested that LAG-3 gene expression was not associated with the prognosis of GBM.However,the expression of LAG-3 gene was negatively correlated with the prognosis of LGG,and the higher its expression level,the worse its prognosis;its high expression in GBM was verified by immunohistochemistry,which was statistically significant;its gene set function was predicted to be related to the response of cells and the body to exogenous stimuli,and exogenous metabolic processes by GO and KEGG pathway enrichment analysis and Gene MANIA database.TIMER database analysis showed that LAG-3 gene expression was weakly correlated with immune cell infiltration as a whole,and the expression level of LAG-3 in tumor tissues was significantly lower,and the corresponding level of immune cell infiltration was lower.Conclusion:1.LAG-3 was highly expressed in glioblastoma tissues,and LAG-3 gene expression levels were not statistically correlated with GBM prognosis,but there was a statistically significant poor prognosis between LAG-3 and LGG.It is instructive for studying GBM.2.The expression of LAG-3 in GBM is correlated with the infiltration of immune cells,which mediates the negative regulation of the immune system.Further study of the function,pathway and mechanism of LAG-3 molecule in tumors is of great significance for carrying out novel therapeutic methods with targets.