Elevated expression of DOK3 indicates high suppressive immune cell infiltration and unfavorable prognosis of gliomas

Abstract Docking protein 3 has been implicated in immune response, including interferon-β production in macrophage and plasma cell differentiation. And its importance in lung adenocarcinoma has been reported. However, studies about its role in gliomas are rare. In this study, we explored the clinical and prognostic characteristics of DOK3 expression in 921 glioma samples. Kaplan-Meier survival analysis and Cox regression analysis verified the independent unfavorable prognostic value and high prognostic accuracy of DOK3 expression for overall survival. Functional analysis with Database for Annotation, Visualization and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) implied the involvement of DOK3 in immune related responses. Immune cell infiltration analysis with online tools, CIBERSORT and EPIC, showed that samples with higher DOK3 expression were infiltrated with much more macrophages. DOK3 was also found to be strongly positively correlated with marker genes of tumor-associated macrophages and M2 macrophages, not M1. Results of immunohistochemical staining also demonstrated that samples with higher DOK3 expression level were infiltrated with more microglia/macrophages and immunosuppressive M2 macrophages. In summary, our results demonstrated the correlation between high DOK3 expression level and malignant progression of gliomas, and the possible involvement of DOK3 in immunosuppressive responses in gliomas.