Neddylation-related gene signature predicts the prognosis and is associated with immune infiltration of glioma

Abstract

Background Glioma is the most prevalent malignant tumor that originates from central nervous system. Neddylation, a post-translational modification similar to ubiquitination, is involved in tumorigenesis and progression. However, there were limited studies focused on the neddylation in glioma. Therefore, we aimed to explore the potential role of neddylation in glioma. Methods In this study, neddylation-related genes (NRGs) were identified and were used to construct a prognostic signature for glioma patients. Based on this prognostic index, we also explored the differences in clinical features, mutational landscape, immune cell infiltration between high-risk and low-risk groups. Next, single-cell RNA sequencing analysis was further performed to verify the expression of these genes in NRG signature. At last, one gene selected from the NRG signature were validated by in vitro experiments. Results Seven genes (TOP2A, F2R, UST, HSPA1B, LGALS3BP, UROS, and OSBPL11) were identified to construct the NRG signature, which was able to successfully classify glioma patients into high-risk and low-risk groups. A nomogram based on the NRG signature and other prognostic factors were developed to accurately predict the prognosis of glioma. Significant differences in prognosis, mutational landscape, immune cell infiltration were found between distinct groups. Moreover, in vitro experiments illustrated that knockdown of HSPA1B could inhibit the proliferation, migration, and invasion of glioma cells and also inhibit the polarization of M2 macrophages. Conclusion These findings provide new insights into understanding the relationship between NRGs and glioma development and identify novel biomarkers may help to guiding precise treatments to glioma.