Multi‐omics technologies and molecular biomarkers in brain tumor‐related epilepsy

• Published in: CNS neuroscience & therapeutics 2024-04, Vol.30 (4), p.e14717-n/a
• Main Authors: Du, Yaoqiang, Li, Rusong, Fu, Danqing, Zhang, Biqin, Cui, Ailin, Shao, Yutian, Lai, Zeyu, Chen, Rongrong, Chen, Bingyu, Wang, Zhen, Zhang, Wei, Chu, Lisheng
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Acetylation; AKT protein; Apoptosis; Astrocytoma; Biological analysis; Biomarkers; Brain cancer; Brain Neoplasms - complications; Brain Neoplasms - genetics; Brain tumors; BTRE; Cell growth; Cell lineage; Convulsions & seizures; Disease; Epilepsy; Epilepsy - complications; Epilepsy - genetics; Forkhead protein; FOXO4 protein; G protein-coupled receptors; Genes; Genetic testing; Genomes; Genomics; Glial cells; Glioma; Glioma - complications; Glioma - genetics; Glioma cells; Humans; Immunohistochemistry; Kinases; Metabolomics; Metastasis; MicroRNAs; miRNA; molecular biomarkers; Multiomics; multi‐omics; Neuronal-glial interactions; Patients; Phosphatidylinositol 3-Kinases; Proteomics; Proto-Oncogene Proteins B-raf; Seizures; Seizures - etiology; TOR protein; Transcriptomics; Tumorigenesis; Tumors
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.14717

Background Brain tumors are one of the leading causes of epilepsy, and brain tumor‐related epilepsy (BTRE) is recognized as the major cause of intractable epilepsy, resulting in huge treatment cost and burden to patients, their families, and society. Although optimal treatment regimens are available, the majority of patients with BTRE show poor resolution of symptoms. BTRE has a very complex and multifactorial etiology, which includes several influencing factors such as genetic and molecular biomarkers. Advances in multi‐omics technologies have enabled to elucidate the pathophysiological mechanisms and related biomarkers of BTRE. Here, we reviewed multi‐omics technology‐based research studies on BTRE published in the last few decades and discussed the present status, development, opportunities, challenges, and prospects in treating BTRE. Methods First, we provided a general review of epilepsy, BTRE, and multi‐omics techniques. Next, we described the specific multi‐omics (including genomics, transcriptomics, epigenomics, proteomics, and metabolomics) techniques and related molecular biomarkers for BTRE. We then presented the associated pathogenetic mechanisms of BTRE. Finally, we discussed the development and application of novel omics techniques for diagnosing and treating BTRE. Results Genomics studies have shown that the BRAF gene plays a role in BTRE development. Furthermore, the BRAF V600E variant was found to induce epileptogenesis in the neuronal cell lineage and tumorigenesis in the glial cell lineage. Several genomics studies have linked IDH variants with glioma‐related epilepsy, and the overproduction of D2HG is considered to play a role in neuronal excitation that leads to seizure occurrence. The high expression level of Forkhead Box O4 (FOXO4) was associated with a reduced risk of epilepsy occurrence. In transcriptomics studies, VLGR1 was noted as a biomarker of epileptic onset in patients. Several miRNAs such as miR‐128 and miRNA‐196b participate in BTRE development. miR‐128 might be negatively associated with the possibility of tumor‐related epilepsy development. The lncRNA UBE2R2‐AS1 inhibits the growth and invasion of glioma cells and promotes apoptosis. Quantitative proteomics has been used to determine dynamic changes of protein acetylation in epileptic and non‐epileptic gliomas. In another proteomics study, a high expression of AQP‐4 was detected in the brain of GBM patients with seizures. By using quantitative RT‐PCR and immunohistochemi