Dataset Information

Molecular and clinical characterization of Galectin-9 in glioma through 1,027 samples.

ABSTRACT: In recent years, research on glioma immunotherapy have grown rapidly. However, the autoimmune-like side effects that are caused by blocking immunological checkpoints hinder their clinical application in gliomas currently. Galectin-9, a ligand for T-cell immunoglobulin mucin 3, has shed a new light on the treatment of malignant glioma. However, the potential mechanism of Galectin-9 is still under discussion. In this study, first, we methodically gathered 1,027 glioma patients with RNA-seq and 986 patients with survival data to explore the role and mechanism of Galectin-9 in gliomas. Second, we analyzed glioma samples from 50 patients in the Department of Neurosurgery, Tianjin Medical University General Hospital. Finally, we found that Galectin-9 was strongly upregulated in glioblastoma multiforme compared with normal brain tissues and lower-grade glioma. Patients with Galectin-9 overexpression had a significantly shorter overall survival. 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. Galectin-9 is more highly expressed in the mesenchymal subtype of glioblastoma multiforme than in the other subtypes. Simultaneously, Galectin-9 was closely associated with the immune response and lymphocyte activation, especially T-cell activation. To further determine the underlying role of Galectin-9 in the immune response, we selected seven immune metagenes. Through cluster analysis and correlation analysis, we discovered that Galectin-9 was highly correlated with immune checkpoint molecules and M2 tumor-associated macrophages. In summary, Galectin-9 serves as a potential therapeutic target to treat glioblastoma multiforme.

SUBMITTER: Yuan F

PROVIDER: S-EPMC7028024 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Molecular and clinical characterization of Galectin-9 in glioma through 1,027 samples.

Yuan Feng F Ming Haolang H Wang Yingshuai Y Yang Yihan Y Yi Li L Li Tao T Ma Haiwen H Tong Luqing L Zhang Liang L Liu Peidong P Li Jiabo J Lin Yu Y Yu Shengping S Ren Bingcheng B Yang Xuejun X

Journal of cellular physiology 20191014 5

In recent years, research on glioma immunotherapy have grown rapidly. However, the autoimmune-like side effects that are caused by blocking immunological checkpoints hinder their clinical application in gliomas currently. Galectin-9, a ligand for T-cell immunoglobulin mucin 3, has shed a new light on the treatment of malignant glioma. However, the potential mechanism of Galectin-9 is still under discussion. In this study, first, we methodically gathered 1,027 glioma patients with RNA-seq and 986 ...[more]

PMID: 31609000

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Project description:Background: PD-L1 has been widely reported as immune check points in a range of malignancies as well as some immune-originated diseases. In glioma, the role of PD-L1 remains unclear. We aimed at investigating its role at transcriptome level and relationship with clinical practice. Method and patients: In total, 976 glioma samples with transcriptome data, including 301 microarray data from Chinese Glioma Genome Atlas (CGGA project) and 675 RNAseq data from TCGA project, were enrolled into our study. Clinical and IDH mutation data were also available. R language was used as the main tool for statistical analysis and graphical work. Results: PD-L1 expression was found to be positively correlated with WHO grade of glioma. PD-L1 seemed to express more in mesenchymal subtype according to TCGA transcriptional classification scheme and may contribute as a potential marker for mesenchymal subtype in glioblastoma. Pearson correlation test indicated that PD-L1 showed robust correlation with PD1, PD-L2, and CD80 in CGGA dataset. Subsequent gene ontology analysis based on significantly correlated genes of PD-L1 revealed that PD-L1 seemed to be profoundly associated with T cell activation. To further investigate the relationship between PD-L1 expression and immune response, we selected a series of immune signatures, which were then transformed into metagenes, and found that PD-L1 expression was particularly paralleled with T-cells and macrophages-related immune response instead of B cell linage-related immune response. In line with the corresponding biological process, PD-L1 exhibited predictive value for glioma patients: Higher PD-L1 indicated significantly shorter survival, especially in glioblastoma. Conclusion: PD-L1 is upregulated in glioblastoma, and is synergistic with other check point members. Moreover, PD-L1 is significantly associated with T-cell activation and macrophage-related immune response and predicts much worse survival for patients, warranting clinical trials of PD1/PD-L1 checkpoint inhibitors for potential glioma treatment.

Project description:BackgroundGlioma is the most common and aggressive type of primary brain tumor in adults. Although radiotherapy and chemotherapy are used in the treatment of glioma, survival remains unsatisfactory. Chemoresistance is one of the primary reasons for the poor prognosis of glioma. Several studies have demonstrated that glioma stem cells (GSC) may be one of the reasons for chemoresistance. In this article, we attempt to search for a new biomarker related to GSC and chemoresistance in glioma.MethodsWe used three datasets (GSE23806, COSMIC, and CGGA) to search for the genes related to GSC, temozolomide (TMZ) resistance, and overall survival. The selected gene was investigated with respect to the relationship between mRNA levels and clinical characteristics in the CGGA and TCGA dataset. Gene ontology (GO) analysis was used for bioinformatics analysis. Kaplan-Meier survival analysis and Cox regression analysis were used for survival analysis.ResultsThe transmembrane protein 71 (TMEM71) gene was selected for further research. TMEM71 was highly expressed in GSCs and TMZ-resistant cells. The TMEM71 mRNA levels increased with increasing grades of glioma. In IDH-wild-type and MGMT-unmethylated samples, TMEM71 was overexpressed. The TMEM71 transcript levels were also increased significantly in mesenchymal subtype gliomas. GO analysis demonstrated that TMEM71 was related to the immune and inflammatory responses, cell proliferation, cell migration, chemotaxis, and the response to drugs. Specifically, PD-1, PD-L1, TIM-3, and B7-H3 were tightly associated with TMEM71 expression. This result indicates that TMEM71 may play an important role in the immune response. More importantly, high expression of TMEM71 was correlated with short survival time in both glioma and glioblastoma patients.ConclusionIn summary, TMEM71 expression was increased in GBM and associated with immune response. Our study suggests that TMEM71 may function as an oncogene and serve as a new effective therapeutic target for the treatment of glioma.

Dataset Information

Molecular and clinical characterization of Galectin-9 in glioma through 1,027 samples.

Publications

Molecular and clinical characterization of Galectin-9 in glioma through 1,027 samples.

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