AUTHOR=Chang Xiaojing , Pan Jie , Zhao Ruoyu , Yan Tianfang , Wang Xinrui , Guo Cunle , Yang Yining , Wang Guohui 

TITLE=DDOST Correlated with Malignancies and Immune Microenvironment in Gliomas

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.917014

DOI=10.3389/fimmu.2022.917014

ISSN=1664-3224

ABSTRACT=Abstract
Among the most common types of brain tumor, gliomas are the most aggressive and have the poorest prognosis. Dolichyl-diphosphooligosaccharide protein glycosyltransferase non-catalytic subunit (DDOST) encodes a component of the oligosaccharide transferase complex and is related to the N-glycosylation of proteins. The role of DDOST in gliomas, however, is not yet known. First, we performed a pan cancer analysis of DDOST in the TCGA cohort. The expression of DDOST was compared between glioma and normal brain tissues in the GEO and CGGA databases. In order to explore the role of DDOST in glioma we analyze the impact of DDOST on the prognosis of glioma patients, the CGGA325 dataset as a test and the CGGA693 dataset as a validation set. Immunohistochemistry was performed on tissue microarrays to examine whether DDOST has an impact on glioma patient survival. Next, using single-cell sequencing analysis, GSEA, immune infiltration analysis, and mutation analysis, we explored how DDOST affect the glioma tumor microenvironment. Finally, we evaluated the clinical significance of DDOST for glioma treatment by constructing nomograms and DCA curves. We found that DDOST was overexpressed in patients with high-grade, IDH wildtype, 1p19q non-codel and MGMT un-methylated which associated with poor prognosis. Patients with high levels of DDOST, regardless of their clinical characteristics, have a worse prognosis. Immunohistochemical analysis confirmed the results of above bioinformatics analysis. Mechanistic analysis revealed that DDOST was closely associated with the glioma microenvironment, especially negatively related to tumor infiltrating B cells, CD4 + T cells and positively related to CAFs and tumor associated macrophages. In conclusion, these findings suggested that DDOST mediated immunosuppressive microenvironment of gliomas and could be an important biomarker in diagnosing and treating gliomas.