SAA1 High Expression Is A Potential Prognostic Marker Of The Tumor Microenvironment In Glioblastoma

Background:The most common primary brain tumor is glioblastoma(GBM),and its prognosis is very poor.Tumor microenvironment(TME)is closely related to the occurrence,development,proliferation,invasion,metastasis and prognosis of tumors.However,TME-related genes and therapeutic targets have not been identified in GBM.Therefore,this study aimed to identify biomarkers associated with TME in GBM with a view to finding new targets for the treatment of this disease.Methods:The stromal and immune cell components of 697 glioma patients in The Cancer Genome Atlas(TCGA)database were calculated by ESTIMAT calculation method of R software.The protein-protein interaction(PPI)network and univariate Cox regression analysis were used to identify hub prognostic genes.Serum amyloid A1 was identified as a related predictor of TME.Subsequently,independent prognostic analysis and a nomogram was constructed to identify SAA1 is an independent prognostic factor.Western blot(WB)and immunohistochemistry(IHC)were utilized to check the expression of SAA1 in both cell lines and tissues.Then,the association between SAA1 and immune cells as well as immune checkpoint genes was analyzed.Finally,gene set enrichment analysis and drug sensitivity analysis were performed.Results:SAA1 expression was significantly higher in GBM than in normal samples and other glioma subtypes,and was negatively correlated with survival.Independent prognostic analysis showed that SAA1 was a prognostic factor associated with TME.In addition,Western blot experiments and IHC showed that SAA1 expression was upregulated in GBM.Subsequently,the overexpression of SAA1 in GBM was confirmed by external validation using the Chinese Glioma Genome Atlas(CGGA)database.GBM gene set enrichment analysis showed that high SAA1 expression was associated with immune regulation,while low SAA1 expression was associated with the regulation of cell activities such as mitosis and cell cycle.CIBERSORT analysis showed that the number of M2 macrophages,neutrophils,activated mast cells,resting mast cells and regulatory T cells in TME was correlated with the expression of SAA1.Finally,the immune checkpoint and drug sensitivity analysis showed that SAA1 up-regulated the expression of immune checkpoint genes LAIR1 and TNFSF14,and the high expression of SAA1 could be used as a drug sensitivity indicator for immunotherapy drugs XAV939,TGX221 and lapatinib.Conclusions:1.SAA1 is a new biomarker for judging TME status and patient survival.2.The biological function of SAA1 at low expression level is mainly to regulate the cell cycle and mitotic process,while the biological function of SAA1 at high expression level is mainly to regulate immune activity.3.In GBM immunotherapy,SAA1 is a drug sensitivity indicator of immunotherapy drugs XAV939,TGX221 and lapatinib,and upregulates the expression of immune checkpoint genes LAIR1 and TNFSF14.