Exploration OfTSPAN32 In Remodeling Immunosuppressive Tumor Microenvironment And As A Potential Biomarker Of Immunotherapy Response In Lung Adenocarcinoma

Objective:This study aims to analyze the genomic data of LUAD and its corres-ponding clinical information through bioinformatics analysis in the existing gene database,and explore the TSPAN32 in combination with gene overexpression,WB,cell proliferation,Trans well experiment,IHC and other related experiments.The potential mechanism of reconstructing the immunosuppressive tumor micro-environment and as a potential biomarker of immunotherapy response in lung adenocarcinoma is expected to provide valuable guidance for the clinical diagnosis,treatment and prognosis of LUAD.Methods:In this study,data downloaded from The Cancer Genome Atlas Program(TCGA)included RNA-seq,phenotype,and survival data.And screen out TSPAN32expression difference genes between LUAD and normal groups,predict the survival period of LUAD patients and the reliability of the results according to the data,and obtain the enrichment results of gene functions and pathways co-expressed with TSPAN32;in order to understand the role of TSPAN32 in the tumor micro-environment(TIME),studied the correlation of TSPAN32 expression with LUAD immune cells,immune cell infiltration and related immune checkpoints,and predicted patient treatment using drug sensitivity analysis and immunotherapy analysis.Finally,through the construction of the TSPAN32 overexpression vector,WB,and IHC related experiments,the reconstruction of the tumor immunotherapy micro-environment by TSPAN32 in LUAD and the correlation analysis and verification in clinical diagnosis,treatment and prognosis were analyzed and verified.Results:This study found that TSPAN32 was significantly under expressed in LUAD compared with normal tissues.This low expression affects multiple genes associated with it,and the enrichment of the functions and pathways of these genes is found to be associated with the triggering of the Ras signaling pathway,and the main downstream pathway of Ras is PI3K/Akt/m TOR,and this pathway The study found that this pathway is the key signaling pathway triggered by the low expression of TSPAN32 in lung adenocarcinoma,and it is also the main cause of the tumor microenvironment of lung adenocarcinoma.It was found that the low expression of TSPAN32 reduced the content of immune cells that mainly kill tumor cells,including monocytes,activated NK cells,CD8~+T cells,resting NK cells,and resting CD4~+memory T cells in LUAD,forming a Immunosuppressive tumor microenvironment(TIME).Immunotherapy analysis found that the TSPAN32 high expression group had significantly better immunotherapy effect than the TSPAN32 low group,and the drug sensitivity analysis of the high and low expression group could serve as an important reference for clinical medication.Conclusion:This study preliminarily found that low expression of TSPAN32 is associated with poor prognosis in patients with LUAD.The low expression of TSPAN32 enhances cell metabolism and division and induces cell carcinogenesis,and the interaction of neuroactive ligand receptors may induce immunosuppressive tumor immune microenvironment,resulting in the reduction of cells that are lethal to cancer cells in immune cells.Further studies are needed to evaluate the potential role of TSPAN32 as a biomarker of LUAD immunotherapy efficacy.In conclusion,this study elucidates the function and mechanism of TSPAN32 in the occurrence and development of LUAD,especially the influence of immune remodeling in the tumor microenvironment,and opens up a new direction for the future diagnosis and treatment of lung adenocarcinoma based on immunotherapy.