DSN1 may predict poor prognosis of lower-grade glioma patients and may be a potential target for immunotherapy

Abstract

Abstract Background: The effect of the DSN1 gene or its methylation in the prognosis, molecular characteristics, and immune cell infiltration of LGG has not yet been revealed. Methods: We obtained 1046 samples from TCGA database, CGGA microarray database, and CGGA RNA-Seq database. A series of bioinformatics methods (GSEA, chi-square test, multivariate, and others) and laboratory validation were used to explore the value of DSN1 in LGG. Results: The results confirmed that the expression levels of DSN1 mRNA and protein in LGG were significantly higher than those in normal brain tissues, and their expression was negatively regulated by its methylation. Moreover, the survival times of patients with low expression of DSN1 and hypermethylation of cg12601032 were significantly prolonged. More importantly, DSN1 was not only a risk factor but also had a good diagnostic value for patient prognosis. It must be emphasized that the expression of DSN1 is related to many kinds of tumor-infiltrating immune cells and has a positive relationship with PD-L1. Furthermore, the GSEA results showed that DSN1 promotes the activation of multiple cancer-related pathways, such as cell cycle. Finally, laboratory results showed knockdown of DSN1significantly inhibited the proliferation and invasion of LGG cells. Conclusions: This study is the first comprehensive analysis of the mechanism of DSN1 leading to poor prognosis of LGG, which provides a new perspective for revealing the pathogenesis of LGG. DSN1 or its methylation not only has diagnostic value for the prognosis of glioma, but may also become a new biological target of anti-tumor immunotherapy.