Mining The Molecular And Clinical Characteristics Of Galectin-9 In Gliomas By High Throughput Sequencing And Bioinformatics

Background: Glioblastomas(GBMs) are the most prevalent and devastating primary Intracranial malignancies.Galectin-9(Gal9) is an important member of the galectin family;it is expressed on lymphocytes and some other cell types.Many studies have demonstrated that galectins not only participate in many physiological processes such as brain development,angiogenesis,T cell homeostasis and feto-maternal tolerance.But also participate in tumor progression,immune escape and tumor angiogenesis.At the same time,there is increasing evidence that galectin-9 demonstrates as a potential prognostic biomarker and a promising treatment target for certain malignancies.However,since the specific mechanism of galectin-9 in GBM remains unclear,an in-depth study of the biological processes of galectin-9 in anti-tumor immunity will provide a molecular basis for targeted galectin-9 therapy.Methods: Through the GEPIA(Gene Expression Profiling Interactive Analysis)visualization website,we analyze the expression of galectin-9 in normal human tissues and various corresponding tumor tissues.Next,we further analyze and study the expression of galectin-9 in different pathological grades of gliomas and different molecular subtypes of GBM in the TCGA and CGGA databases.Secondly,we analyzed glioma samples from 50 patients in the Department of Neurosurgery,Tianjin Medical University General Hospital by immunohistochemistry.To further explore the specific immune response of galectin-9,through cluster analysis and correlation analysis,we analyzed the relationship between galectin-9 and seven gene-sets that represent different types of immune response functions and defined them as metagenes.Results: Compared with control brain tissue and low-grade gliomas,galectin-9 is highly expressed in glioma patients,and the higher the grade,the higher the expression,and the highest expression in GBM patients.At the same time,galectin-9 is highly expressed in interstitial glioblastoma,and the survival time of glioma patients with high expression of galectin-9 is significantly lower than that of patients with low expression of galectin-9.Moreover,the tissue microarray data displayed that the expression of galectin-9 in the core of tumor is higher than that in the border,and was correlated with the shorter survival in glioma patients.Through bioinformatic analyses,we discovered that galectin-9 was highly correlated with immune checkpoint molecules and M2 tumor-associated macrophages.Conclusions:Galectin-9 was overexpressed in GBM samples compared with normal brain controls.Moreover,the tissue microarray data displayed that the expression of galectin-9 in the core of tumor is higher than that in the border.In addition,by analyzing the relationship between galectin-9 and immune function-related gene sets,we found that galectin-9 expression was positively correlated with immune checkpoint molecules and M2 tumor-associated macrophage markers.Galectin-9 is likely to exert tumor immunosuppression or immune escape through M2 tumor-associated macrophages.This study provides a new insight that galectin-9 may be a new immunotherapy target for GBM.