Clinical Significance And Mechanism Of CCL8 Expression In Glioma

Background:Glioma is the most common malignant tumor of the central nervous system,with the characteristics of high recurrence and high mortality.Although the standard treatment of gliomas takes many forms,including surgery,chemotherapy and radiotherapy,the survival time is still very short.Glioblastoma is the most malignant tumor(Glioblastoma,GBM,WHO grade ?)with the median survival time less than 15 months.Based on the clinical challenges faced in the treatment of gliomas,there is an urgent need to find new treatments to improve clinical effect.Chemokines are a class of small molecule proteins that can be secreted extracellularly.Their main role is to regulate the chemotaxis and recruitment of immune cells and play a key role in tumorigenesis and development.Many studies have shown that they can be used to improve the effectiveness of tumor immunotherapy.CC chemokine ligand 8(CCL8),also known as monocyte chemoattractant protein-2(MCP-2),is a member of the CC chemokine family.The current research found that CCL8 is abnormally expressed in breast cancer,melanoma and other malignant tumor tissues,and is closely related to the occurrence and development of various malignant tumors.However,the expression and clinical significance of CCL8 in glioma tissues are unclear.Therefore,it is very important to explore the expression and clinical significance of chemokine CCL8 in gliomas.Objective:To explore the clinical significance and mechanism of CCL8 expression in glioma.Methods:1.qRT-PCR was used to detect the expression level of CCL8 in glioma tissues;2.Using CGGA(Chinese Glioma Genome Atlas),TCGA(The Cancer Genome Atlas)database and clinical specimens,we analyzed the relationship between CCL8 expression level in samples and WHO classification;3.We analyzed the relationship between CCL8 expression level and isocitrate dehydrogenase(IDH)mutations in CGGA and TCGA database and the diagnostic value for IDH wild-type(IDH WT)in gliomas;4.We analyzed the relationship between CCL8 expression level and glioma molecular subtypes in CGGA and TCGA database and the diagnostic value for mesenchymal subtype;5.We analyzed the relationship between CCL8 expression level and genes related to immune function in CGGA database;6.We analyzed the relationship between CCL8 expression level and T cell function in CGGA and TCGA databases;7.We analyzed the relationship between CCL8 expression level and macrophage function in CGGA and TCGA databases;8.We analyzed the relationship between CCL8 expression level and tumor-associated macrophages in TCGA database;9.Using TCGA database,we analyzed the relationship between CCL8 expression level and the prognosis of glioma patients.Results:1.Compared with low grade glioma(LGG),the expression level of CCL8 in glioblastoma is significantly increased.2.In the CGGA and TCGA databases,the expression level of CCL8 in GBM is significantly increased compared with WHO II and III glioma.3.Compared with IDH mutant-type(IDH-Mut)glioma,the expression level of CCL8 in IDH-WT glioma is significantly increased,and it has diagnostic value for IDH-WT glioma.4.Compared with other molecular subtypes of glioma,the expression of CCL8 in mesenchymal subtype glioma is significantly increased,and it has diagnostic value for mesenchymal glioma.5.The expression level of CCL8 in glioma is positively correlated with gene clusters representing macrophage function and T cell function.6.CCL8 is positively correlated with T cell activation,cytokine production and immune response,but negatively correlated with T cell-mediated immune response to tumor cells.7.CCL8 is positively correlated with macrophage activation,differentiation and cytokine production.8.The expression level of CCL8 in glioma is closely related to the tumor-associated macrophages.9.The average survival time of glioma patients in the CCL8 high expression group was significantly lower than that in the low expression group.Conclusion:1.The expression level of CCL8 in glioma is closely related to its malignant phenotype.2.The expression level of CCL8 in glioma was positively correlated with M2 macrophage infiltrating in tumor tissue.3.The increased expression of CCL8 in gliomas indicates the poor prognosis of patients.