Novel roles of VAT1 expression in the immunosuppressive action of diffuse gliomas.

Affiliation

Yang P(1)(2)(3), Wang K(4)(2)(3), Zhang C(1)(2)(3), Wang Z(1)(2)(3), Liu Q(1), Wang J(1), Jiang T(5)(6)(7)(8)(9), Shan X(10)(11)(12).
Author information:
(1)Department of Neurosurgery, Fengtai District, Beijing Tiantan Hospital, Capital Medical University, 119 South 4th Ring Road West, Beijing, 100070, China.
(2)Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
(3)Chinese Glioma Genome Atlas Network
(CGGA), Beijing, China.
(4)Department of Gamma Knife, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
(5)Department of Neurosurgery, Fengtai District, Beijing Tiantan Hospital, Capital Medical University, 119 South 4th Ring Road West, Beijing, 100070, China. [Email]
(6)Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. [Email]
(7)Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China. [Email]
(8)China National Clinical Research Center for Neurological Diseases, Beijing, China. [Email]
(9)Chinese Glioma Genome Atlas Network
(CGGA), Beijing, China. [Email]
(10)Department of Radiotherapy, Fengtai District, Beijing Tiantan Hospital, Capital Medical University, 119 South 4th Ring Road West, Beijing, 100070, China. [Email]
(11)Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. [Email]
(12)Chinese Glioma Genome Atlas Network
(CGGA), Beijing, China. [Email]

Abstract

Standard treatment regimen of gliomas has almost reached a bottleneck in terms of survival benefit. Immunotherapy has been explored and applied in glioma treatment. Immunosuppression, as a hallmark of glioma, could be alleviated by inhibiting certain abnormally expressed biomarkers. Here, transcriptome data of 325 whole grade gliomas were collected from the CGGA database. The TCGA RNA sequencing database was used for validation. Western blot was used to verify the expression level of VAT1 on cellular level. The results showed that the expression of VAT1 was positively correlated with the grades of glioma as classified by WHO. A higher expression level of VAT1 was observed in the mesenchymal subtype of gliomas. The area under the curve suggested that the expression level of VAT1 might be a potential prognostic marker of mesenchymal subtype. In survival analysis, we found that patients with high VAT1 expression level tended to have shorter overall survival, which indicated the prognostic value of VAT1 expression. The results of gene ontology analysis showed that most biological processes of VAT1-related genes were involved in immune and inflammatory responses. The results of GSEA analysis showed a negative correlation between VAT1 expression and immune cells. We also identified that the expression of immune checkpoints increased with VAT1 expression. Therefore, the high expression level of VAT1 in patients with glioma was a potential indicator of a lower survival rate for patients with gliomas. Remarkably, VAT1 contributed to glioma-induced immunosuppression and might be a novel target in glioma immunotherapy.