Expression of RINT1 predicts seizure occurrence and outcomes in patients with low-grade gliomas.

Abstract

Most patients with low-grade gliomas (LGGs) experience epileptic seizures as an initial symptom. However, the mechanism of LGG-related epilepsy is poorly understood. Genetic changes in brain tumors influence epileptic seizures, but few biomarkers have been associated with LGG-related seizures. We investigated the association between LGG-related epilepsy and tumor-specific molecular changes. Clinical characteristics, RNA sequence data, and case follow-up data were reviewed for 76 patients with histologically confirmed LGG. Gene expression (n = 21,469) was compared between patients with preoperative epileptic seizures and those without preoperative epileptic seizures. The Engel classification was used at 6 months after surgery to evaluate the prognostic role of genes that passed the screen. Expression of RAD50 interactor 1 (RINT1) significantly differed between LGG patients with and without preoperative epileptic seizures (p = 0.003). This result was validated by applying the same analysis to RNA sequence data from The Cancer Genome Atlas (p = 0.048). Patients with high RINT1 expression were at increased risk of LGG-related seizures compared to those with low expression (p = 0.044). RINT1 was also identified as a predictor of seizure outcomes in patients with LGG at 6 months after tumor resection (p = 0.022). Our results suggest that high RINT1 expression may represent a risk factor for LGG-related seizures and may be associated with seizure outcomes.