No abstract

Histone acetyltransferase 1 (HAT1) is a key regulatory molecule in histone acetylation and promotes cancer malignancy. This study aimed to reveal the role of HAT1 in lower-grade gliomas (LGGs) and the potential mechanism by which it mediates pathological processes. We collected transcriptome data and detailed clinicopathological features of 906 LGG patients through TCGA RNA-seq and CGGA RNA-seq. Subsequently, various bioinformatics and molecular biology methods were used to reveal the impact of HAT1 on the prognosis, clinical characteristics, regulatory mechanism, and the potential value of antitumor immunotherapy in patients with LGG. RT-qPCR and immunohistochemistry showed that the expression level of HAT1 protein or mRNA in LGG tissue was significantly higher than that in non-tumor brain tissue. Furthermore, there is a positive expression relationship between HAT1 and clinical malignant patient characteristics such as IDH-wild and recurrent types. Kaplan–Meier and Cox regression revealed that high HAT1 expression could be used as an independent risk factor for reduced overall survival of patients. GSEA analysis showed that HAT1 overexpression promotes the activation of the cell cycle, adherens junctions, and RIG-I-like receptor signaling pathways in LGG. Finally, the TIMER database showed that HAT1 could promote the increase in multiple immune cell infiltration levels and showed a positive expression relationship with immune checkpoints in LGG. This study provides a potentially high-value target for the antitumor immunotherapy of LGG patients. For the first time, we explain the influence and mechanism of HAT1 on the prognosis of LGG patients to gain insights into the pathogenesis of LGG.

Background: Traumatic brain injury (TBI) as a pathogenetic factor in glioma remains controversial, and currently there is still no clear mechanism behind post-TBI glioma. Thus, we provide two case reports of post-TBI glioma contributing power to this research, and we provide a summary of the mechanisms of post-TBI glioma through literature review. Methods: We report two cases of brain gliomas that developed in the scar of a previous brain trauma. Both patients were male and both had suffered prior traumatic brain injuries (time interval 10–20 years), and postoperative pathological findings reported glioblastoma and WHO grade III glioma, respectively. Results: These two cases further support the association of between traumatic brain injury and gliomas development. Conclusion: Although the epidemiological investigation between TBI and glioma is still controversial, there are still some important aspects here that can determine the possibility between TBI and gliomagenesis. Besides, we found that the reparative response of neural stem cells and the dysregulation of inflammatory cells are timportant theories of the mechanism of post-TBI glioma.

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.