Abstract
Background
Glioma-related epilepsy (GRE) is a common symptom in patients with diffuse gliomas. However, the underlying mechanisms of GRE remain unclear. The current study aimed to investigate the underlying epileptogenic mechanisms of GRE through RNA sequencing analysis.
Methods
Demographic, RNA sequencing, and follow-up data of 643 patients were reviewed. Patients were divided into test and validation groups (223 and 420 patients, respectively) by different time periods for RNA sequencing. The differentially expressed genes (DEGs) associated with preoperative GRE were identified using R software. Functional enrichment analysis was subsequently performed, and tissue-infiltrating immune cells were also estimated. Weighted correlation network analysis (WGCNA) was conducted to further identify key modules exhibiting the highest correlation with preoperative GRE. Overlapping genes between the DEG set and key gene set identified by WGCNA were selected and verified in the validation cohort. The protein–protein interaction (PPI) network analysis was then constructed to identify hub genes for preoperative GRE.
Results
A total of 219 DEGs were identified, among which 112 were upregulated and 107 downregulated in patients with GRE. Functional enrichment analysis revealed that upregulated DEGs were related to ion channel activity, while downregulated genes were related to immunity. Forty-two genes were further selected from overlapping DEGs and the key gene set. Among these genes, 31 genes showed significant differences in the validation cohort. Finally, the PPI network analysis identified six genes, including SCN3B, KCNIP2, KCNJ11, VEGFA, MMP9, and ANXA2, as hub genes for GRE.
Conclusion
The current study revealed that ion channel activity and immunity dysfunction in diffuse glioma patients contributed to the occurrence of GRE, and SCN3B might be a shared therapeutic target for both diffuse gliomas and GRE. These findings could improve the understanding of the mechanisms of GRE and promote individualized medications for glioma management.
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Funding
This work was supported by the National Natural Science Foundation of China [grant number, 82001777, XF]; the Public welfare development and reform pilot project of Beijing Medical Research Institute [grant number, JYY 2019-5, TJ]; the CAMS Innovation Fund for Medical Sciences [grant number, 2019- I2M-5-021, TJ] and the Beijing Nova Program [grant number, Z181100006218064, YW].
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LL and XF: study concept and design. LL, CBZ and ZW: data acquisition and analysis. LL and XF: formal analysis and investigation. LL and GYH: writing-original draft preparation. XF: writing-review and editing. YW, XF and TJ: funding acquisition. XF and TJ: supervision. All authors contributed to the article and approved the submitted version.
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The studies involving human participants were reviewed and approved by the Ethics Committee of Beijing Tiantan Hospital. The patients/participants provided their written informed consent to participate in this study.
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Li, L., Zhang, C., Wang, Z. et al. Expression changes in ion channel and immunity genes are associated with glioma-related epilepsy in patients with diffuse gliomas. J Cancer Res Clin Oncol 148, 2793–2802 (2022). https://doi.org/10.1007/s00432-022-04049-3
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DOI: https://doi.org/10.1007/s00432-022-04049-3