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

J Cancer Res Clin Oncol. 2015 Apr;141(4):729-34. doi: 10.1007/s00432-014-1827-8. Epub 2014 Oct 11.

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: Our results suggest that high RINT1 expression may represent a risk factor for LGG-related seizures and may be associated with seizure outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Cycle Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genetic Predisposition to Disease / genetics*
  • Glioma / complications
  • Glioma / genetics*
  • Glioma / surgery
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Predictive Value of Tests
  • Preoperative Period
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Seizures / complications
  • Seizures / genetics*
  • Treatment Outcome
  • Young Adult

Substances

  • Cell Cycle Proteins
  • RINT1 protein, human
  • RNA, Messenger