The Significance Of BTN3A3 Gene Expression In Non-small Cell Lung Cancer

Background:The butyrophilin(BTN)family has many members with diverse functions related to immunomodulation,initiation and progression of tumors.The extracellular domain of BTN family members is the same as B7 family members and which is considered to be B7 family related proteins,suggesting that the BTN family may have similar immunomodulatory functions.Existing studies have shown that the BTN family members are expressed on a variety of tumor cells and participate in the occurrence and development of tumors.BTN3A3 is a member of the BTN family.Indepth study of the expression of BTN3A3 molecule in non-small cell lung cancer(NSCLC),the effect of the change of BTN3A3 molecule expression on the biological behavior of NSCLC and its role in tumor microenvironment(TME)is significant for understanding the mechanism of occurrence and development of NSCLC,the interaction between tumor cells and immune cells and its effect on the prognosis.Methods:The expression of BTN3A3 gene in NSCLC tissue was detected by RTqPCR.Small interference RNA knockdown BTN3A3 gene and the overexpression vectors of BTN3A3 gene were constructed and transfected into NSCLC cell lines.After knocking down and overexpressing BTN3A3 gene,the proliferation,migration and invasion ability of NSCLC cells were analyzed.The expression of BTN3A3 protein on the surface of NSCLC cells was quantitatively analyzed by multiplex immunofluorescence staining technique to explore the relationship between the difference of BTN3A3 protein expression on tumor cells and the clinical characteristics of the patients.The correlation between tumor cells expressing BTN3A3 protein and immune cell infiltration and the relationship between BTN3A3 expression in the TME and the prognosis of NSCLC patients was analyzed.Results:The expression level of BTN3A3 gene in tumor tissue was significantly lower than that in adjacent normal tissue.Patients with low expression of BTN3A3 gene showed later clinical stage and lower degree of tumor differentiation.After knocking down the expression level of BTN3A3 gene,the proliferation,migration and invasion ability of NSCLC cells were significantly enhanced.On the contrary,the proliferation,migration and invasion ability of NSCLC cells decreased after overexpression of BTN3A3 gene.In the TME,BTN3A3 protein expression was related to the clinicopathological features of the patients,and the patients with low expression of BTN3A3 protein showed later clinical stage and lower tumor differentiation degree,the infiltration of high density of CD8+T cells in the tumor area of the tumor tissue was related to the better prognosis of patients with NSCLC,while the density of BTN3A3+tumor cells was positively correlated with the density of CD8+T cells in the tumor area of the tumor tissue,and the survival time of patients with high expression of BTN3A3 protein was longer.Conclusion:The change of BTN3A3 gene expression plays a key role in the occurrence and development of NSCLC;The decrease of BTN3A3 expression level is related to the poor prognosis of NSCLC patients;In vitro cell experiments,the results showed that the decreased expression level of BTN3A3 promoted the proliferation,invasion and migration of NSCLC cells,and the patients with low expression of BTN3A3 showed a higher level of invasive phenotype.The expression of BTN3A3 protein is positively correlated with the infiltration of CD8+T lymphocytes in the tumor area of the tumor tissue,which may be an important factor affecting the long-term survival of patients.