Analysis Of The Expression Characteristics And Clinical Significance Of SPP1 In Gliomas Based On Transcriptome Data

Background:Glioma is the most common malignant tumor of the central nervous system,accounting for more than 80%of intracranial malignant tumors.However,due to unclear tumor boundaries and resistance to radiotherapy and chemotherapy,some patients still cannot obtain an ideal prognosis even though they have undergone surgical resection and postoperative radiotherapy and chemotherapy.The tumor microenvironment is composed of tumor cells,a variety of non-tumor cells and extracellular matrix.Macrophages/microglia,dendritic cells,neutrophils,and T cells are the main immune cells in the microenvironment.With the deepening of research on gliomas,immune-related factors have been found to play an important role in the progression and resistance of gliomas.Some molecular markers have also been used to guide the diagnosis and treatment of gliomas.Finding the key molecules for the occurrence and development of glioma has become a research hotspot.Objectives:The transcriptome data and clinical data of 2263 patients with glioma were analyzed to find the key molecules for the malignant progression of glioma,and to provide a new theoretical basis for the comprehensive treatment of glioma.Methods:The RNA-seq data included from the Chinese Glioma Genome Atlas(CGGA)and The Cancer Genome Atlas(TCGA)were analyzed by gene set variation analysis(GSVA)to score a variety of immune cell infiltration.According to the different infiltration levels of multiple immune cells,the unsupervised clustering method was used to cluster the patients with high-grade glioma and the patients with low-grade glioma,and the survival analysis of the subgroups was performed.Differential genes were screened according to diferent levels of immune cell infiltration,combined with the results of protein interaction network analysis(PPI),and survival analysis to screen out the target gene SPP1.The gene microarray data of CGGA and GSE16011 were then included to analyze the expression level of SPP1 in different groups of gliomas,the relationship between SPP1 expression and the degree of immune cell infiltration,and the correlation between SPP1 expression and immune checkpoint gene expression.Screen the genes related to SPP1 expression for gene ontology(GO)biological process enrichment analysis,and gene set enrichment analysis(GSEA)to find the gene set enriched by the differentially expressed genes of the SPP1 high expression group compared with the low expression group.Finally,the Kaplan-Meier survival curve and Log-Rank test were combined with univariate and multivariate Cox analysis to study the effect of SPP1 expression on the survival of glioma patients;and draw ROC curves to verify the efficacy of SPP1 expression in predicting the prognosis of patients.Results:1.Both GBM and LGG glioma can be divided into different subgroups according to different infiltration levels of various immune cells and have different prognostic differences.2.SPP1 is highly expressed in glioblastoma,mesenchymal glioma,IDH-wt type glioma with higher malignancy.3.In patients with GBM and LGG,the expression of SPP1 is positively correlated with the infiltration of macrophages,activated dendritic cells,and follicular helper T cells in glioma,and The expression of SPP1 is positively correlated with the expression of multiple immune checkpoint genes.4.The biological processes of SPP1 and its related genes are enriched in various immune responses such as neutrophil activation.The differential gene set of the SPP1 high expression group is enriched in JAK/STAT and Toll-like receptor pathways.5.Among GBM and LGG patients,the prognosis of patients with high SPP1 expression is poor,and SPP1 expression is an independent factor influencing the prognosis of glioma patients.Conclusions:1.Both high-grade glioma and low-grade glioma can be divided into different subgroups according to the different infiltration levels of multiple immune cells,and there are differences in prognosis.2.SPP1 and its related genes are involved in a variety of immune response processes.The expression of SPP1 in gliomas is related to the expression of multiple checkpoint genes and the level of multiple immunosuppressive cell infiltration,which may be a potential therapeutic target.3.The expression of SPP1 in gliomas is positively correlated with the degree of malignancy.The expression of SPP1 is an independent factor affecting the prognosis of patients with gliomas and can be used as a predictor of the prognosis of patients with gliomas.