FOXO4 expression is associated with the occurrence and outcome of seizures: An RNA-sequencing analysis of low-grade gliomas.

PURPOSE: Epileptic seizures account for most of the initial symptoms in patients with low-grade gliomas (LGGs). Nevertheless, the molecular mechanisms of tumor-associated seizures remain unclear. This study investigated the genetic changes associated with the occurrence and outcome of seizures in patients with LGGs.

METHODS: The clinical characteristics and gene profile data of 86 patients with LGGs were collected from the Chinese Glioma Genome Atlas database. Gene expression was analyzed based on whole-genome RNA sequencing. The genes with significantly different expressions between patients with and without seizures were identified. Additionally, the Engel Epilepsy Surgery Outcome Scale was applied to evaluate the seizure outcomes at 6 months after tumor resection.

RESULTS: In patients with LGGs, the expression of Forkhead Box O4 (FOXO4) was significantly different between the seizure and non-seizure groups, and high FOXO4 expression was found to be associated with a low risk of seizure occurrences (p=0.026). This result was validated by using the clinical information and RNA sequence data from The Cancer Genome Atlas database (p=0.005). FOXO4 was additionally identified as a predictor of seizure outcomes in patients with LGGs at 6 months after tumor resection (p=0.018).

CONCLUSIONS: The results of our genomic analysis suggest that low FOXO4 expression is a significant risk factor for epileptic seizures in patients with LGGs and is associated with the seizure outcome. FOXO4 may be a potential therapeutic target for tumor-associated epilepsy.