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

Abstract

DSN1 has been previously found to be positively correlated with various cancers. However, the effect of DSN1 or its methylation on the prognosis, molecular characteristics, and immune cell infiltration of low-grade glioma (LGG) has not yet been studied. We obtained 1046 LGG samples from the The Cancer Genome Atlas, The Chinese Glioma Genome Atlas (CGGA) microarray, and CGGA RNA-Seq databases. Bioinformatic methods (gene set enrichment analysis (GSEA), chi-square test, multivariate), and laboratory validation were used to investigate DSN1 in LGG. The expression levels of DSN1 mRNA and protein in LGG were substantially higher than those in normal brain tissue, and their expression was negatively regulated by methylation. The survival time of patients with low expression of DSN1 and cg12601032 hypermethylation was considerably prolonged. DSN1 was a risk factor, and of good diagnostic and prognostic value for LGG. Importantly, the expression of DSN1 is related to many types of tumor-infiltrating immune cells and has a positive correlation with PDL1. DSN1 promoted the activation of multiple cancer-related pathways, such as the cell cycle. Additionally, knockdown of DSN1 substantially inhibited the proliferation and invasion of LGG cells. To the best of our knowledge, 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 has diagnostic value for the prognosis of glioma, and may become a new biological target of anti-tumor immunotherapy.

Keywords

• Low-grade glioma
• DSN1
• biomarker
• prognosis
• immunotherapy